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Kobara YM, Akpan IJ, Nam AD, AlMukthar FH, Peter M. Artificial Intelligence and Data Science Methods for Automatic Detection of White Blood Cells in Images. JOURNAL OF IMAGING INFORMATICS IN MEDICINE 2025:10.1007/s10278-025-01538-y. [PMID: 40379861 DOI: 10.1007/s10278-025-01538-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 04/29/2025] [Accepted: 04/30/2025] [Indexed: 05/19/2025]
Abstract
Data scieQuerynce (DS) methods and artificial intelligence (AI) are critical in today's healthcare services operations. This study focuses on evaluating the effectiveness of AI and DS in biomedical diagnostics, including automatic detection and counting of white blood cells (WBCs) and types, which provide valuable information for diagnosing and treating blood diseases such as leukemia. Automating these tasks using AI and DS saves time and avoids or minimizes errors compared to manual processes, which can be complex and error prone. The study utilizes bibliographic data from SCOPUS to evaluate research on applying AI algorithms and DS methods for mapping and classifying WBC images for treatment of blood diseases, such as leukemia using literature survey and science mapping methodology. The results show the potency of different DS methods and AI algorithms, such as machine learning, deep learning, and classification algorithms that enable the automatic detection of WBC images. AI and DS algorithms offer critical benefits in effectively and efficiently analyzing microscopic images of blood cells. The automatic identification, localization, and classification of WBCs speed up the patient diagnosis process, allowing hematologists to focus on interpreting results. Automatic processes identify specific abnormalities and patterns, enhancing accuracy and timely diagnoses. Future work will examine the application of generative AI in blood cells diagnostics.
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Affiliation(s)
- Yawo M Kobara
- Odette School of Business, University of Windsor, Windsor, ON, Canada
| | - Ikpe Justice Akpan
- Department of Information Systems and Business Analytics, Kent State University, 800 E. Summit Street, Kent, OH, 44242, USA.
| | - Alima Damipe Nam
- Residency Program, National Institute of Hygiene, University of Lomé, Lome, Togo
| | - Firas H AlMukthar
- Department of Information Technology, Catholic University in Erbil, Erbil, Kurdistan Region, Iraq
| | - Mbuotidem Peter
- Healthcare Research Group, Ibom International Center for Research and Scholarship, Windsor, ON, Canada
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Ismahil MA, Zhou G, Rajasekar S, Gao M, Bansal SS, Patel B, Limdi N, Xie M, Antipenko S, Rokosh G, Hamid T, Prabhu SD. Splenic CD169 +Tim4 + Marginal Metallophilic Macrophages Are Essential for Wound Healing After Myocardial Infarction. Circulation 2025. [PMID: 40289811 DOI: 10.1161/circulationaha.124.071772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 03/31/2025] [Indexed: 04/30/2025]
Abstract
BACKGROUND Fidelity of wound healing after myocardial infarction (MI) is an important determinant of subsequent adverse cardiac remodeling and failure. Macrophages derived from infiltrating Ly6Chi (lymphocyte antigen 6 complex, locus C) blood monocytes are a key component of this healing response; however, the importance of other macrophage populations is unclear. METHODS We used a variety of in vivo murine models and orthogonal approaches, including surgical MI, flow cytometry and single-cell RNA sequencing, lineage tracing and cell tracking, splenectomy, parabiosis, cell adoptive transfer, and functional characterization, to establish an essential role for splenic CD169+Tim4+ (cluster of differentiation 169+; T cell immunoglobulin- and mucin-domain-containing molecule 4) marginal metallophilic macrophages (MMMs) in post-MI wound healing in mice. Flow cytometry was used to measure circulating CD169+Tim4+ monocytes in humans with ST-segment-elevation MI and control participants with stable coronary artery disease undergoing elective percutaneous coronary intervention. RESULTS Splenic CD169+Tim4+ MMMs circulate in blood as Ly6Clow monocytes expressing macrophage markers and help populate CD169+Tim4+CCR2-LYVE1low macrophages in the naive heart. After acute MI, splenic MMMs augment phagocytosis and CCR (C-C motif chemokine receptor) 3 and CCR4 expression, and robustly mobilize to the heart, resulting in marked expansion of cardiac CD169+Tim4+LYVE1low macrophages with an immunomodulatory and proresolving gene signature. These macrophages are obligatory for apoptotic neutrophil clearance, suppression of inflammation, and induction of a reparative macrophage phenotype in the infarcted heart. Splenic MMMs are both necessary and sufficient for post-MI wound healing, and limit late pathological remodeling. Liver X receptor-α agonist-induced expansion of the splenic marginal zone and MMMs during acute MI alleviates inflammation and improves short- and long-term cardiac remodeling. Humans with acute ST-segment-elevation MI also exhibit expansion of circulating CD169+Tim4+ cells, primarily within the intermediate (CD14+CD16+) monocyte population. CONCLUSIONS Splenic CD169+Tim4+ MMMs are required for proresolving and reparative responses after MI and can be manipulated for therapeutic benefit to limit long-term heart failure.
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Affiliation(s)
- Mohamed Ameen Ismahil
- Division of Cardiology, Department of Medicine, Washington University in St Louis, MO (M.A.I., S.R., G.R., T.H., S.D.P.)
- Departments of Medicine, Cardiovascular Disease (M.A.I., G.Z., M.G., S.S.B., B.P., M.X., S.A., G.R., T.H., S.D.P.), University of Alabama at Birmingham
| | - Guihua Zhou
- Departments of Medicine, Cardiovascular Disease (M.A.I., G.Z., M.G., S.S.B., B.P., M.X., S.A., G.R., T.H., S.D.P.), University of Alabama at Birmingham
| | - Shreya Rajasekar
- Division of Cardiology, Department of Medicine, Washington University in St Louis, MO (M.A.I., S.R., G.R., T.H., S.D.P.)
| | - Min Gao
- Departments of Medicine, Cardiovascular Disease (M.A.I., G.Z., M.G., S.S.B., B.P., M.X., S.A., G.R., T.H., S.D.P.), University of Alabama at Birmingham
| | - Shyam S Bansal
- Departments of Medicine, Cardiovascular Disease (M.A.I., G.Z., M.G., S.S.B., B.P., M.X., S.A., G.R., T.H., S.D.P.), University of Alabama at Birmingham
| | - Bindiya Patel
- Departments of Medicine, Cardiovascular Disease (M.A.I., G.Z., M.G., S.S.B., B.P., M.X., S.A., G.R., T.H., S.D.P.), University of Alabama at Birmingham
| | - Nita Limdi
- Neurology (N.L.), University of Alabama at Birmingham
| | - Min Xie
- Departments of Medicine, Cardiovascular Disease (M.A.I., G.Z., M.G., S.S.B., B.P., M.X., S.A., G.R., T.H., S.D.P.), University of Alabama at Birmingham
| | - Sergey Antipenko
- Departments of Medicine, Cardiovascular Disease (M.A.I., G.Z., M.G., S.S.B., B.P., M.X., S.A., G.R., T.H., S.D.P.), University of Alabama at Birmingham
| | - Gregg Rokosh
- Division of Cardiology, Department of Medicine, Washington University in St Louis, MO (M.A.I., S.R., G.R., T.H., S.D.P.)
- Departments of Medicine, Cardiovascular Disease (M.A.I., G.Z., M.G., S.S.B., B.P., M.X., S.A., G.R., T.H., S.D.P.), University of Alabama at Birmingham
| | - Tariq Hamid
- Division of Cardiology, Department of Medicine, Washington University in St Louis, MO (M.A.I., S.R., G.R., T.H., S.D.P.)
- Departments of Medicine, Cardiovascular Disease (M.A.I., G.Z., M.G., S.S.B., B.P., M.X., S.A., G.R., T.H., S.D.P.), University of Alabama at Birmingham
| | - Sumanth D Prabhu
- Division of Cardiology, Department of Medicine, Washington University in St Louis, MO (M.A.I., S.R., G.R., T.H., S.D.P.)
- Departments of Medicine, Cardiovascular Disease (M.A.I., G.Z., M.G., S.S.B., B.P., M.X., S.A., G.R., T.H., S.D.P.), University of Alabama at Birmingham
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Wang M, Wang Z, Li Z, Qu Y, Zhao J, Wang L, Zhou X, Xu Z, Zhang D, Jiang P, Fan B, Liu Y. Targeting programmed cell death in inflammatory bowel disease through natural products: New insights from molecular mechanisms to targeted therapies. Phytother Res 2025; 39:1776-1807. [PMID: 38706097 DOI: 10.1002/ptr.8216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 03/14/2024] [Accepted: 04/11/2024] [Indexed: 05/07/2024]
Abstract
Inflammatory bowel disease (IBD) is an autoimmune disorder primarily characterized by intestinal inflammation and recurrent ulceration, leading to a compromised intestinal barrier and inflammatory infiltration. This disorder's pathogenesis is mainly attributed to extensive damage or death of intestinal epithelial cells, along with abnormal activation or impaired death regulation of immune cells and the release of various inflammatory factors, which contribute to the inflammatory environment in the intestines. Thus, maintaining intestinal homeostasis hinges on balancing the survival and functionality of various cell types. Programmed cell death (PCD) pathways, including apoptosis, pyroptosis, autophagy, ferroptosis, necroptosis, and neutrophil extracellular traps, are integral in the pathogenesis of IBD by mediating the death of intestinal epithelial and immune cells. Natural products derived from plants, fruits, and vegetables have shown potential in regulating PCD, offering preventive and therapeutic avenues for IBD. This article reviews the role of natural products in IBD treatment by focusing on targeting PCD pathways, opening new avenues for clinical IBD management.
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Affiliation(s)
- Mengjie Wang
- The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Zhiyuan Wang
- People's Hospital of Zhengzhou, Zhengzhou, China
| | - Zhichao Li
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yuan Qu
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Jiting Zhao
- The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Lei Wang
- The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xinpeng Zhou
- The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ziqi Xu
- The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Di Zhang
- The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ping Jiang
- Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Bing Fan
- The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ying Liu
- The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
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Freitas MSE, García HDM, Fiala-Rechsteiner SMDE, Fontes CS, Teixeira CS, Viana JHM, Albino MV, Costa LMLD, Carneiro GF, Ribeiro GC, Sancler-Silva YFR. Is platelet-rich plasma effective in treating uterine inflammation in jennies inseminated with cryopreserved donkey semen? Theriogenology 2025; 231:144-153. [PMID: 39454479 DOI: 10.1016/j.theriogenology.2024.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 10/01/2024] [Accepted: 10/12/2024] [Indexed: 10/28/2024]
Abstract
Despite frozen donkey semen demonstrating high quality after thawing and achieving suitable pregnancy rates in mares, it yields unsatisfactory results in jennies, likely due to a stronger uterine inflammatory response. This study assessed the effects of platelet-rich plasma (PRP) on uterine inflammation and pregnancy rates in jennies inseminated with frozen donkey semen. Estrous cycles from 11 jennies were assigned to three groups: Control (CTR, n = 22) with no treatment; Single PRP infusion (S-PRP, n = 22) administered 30 h after ovulation induction, prior to artificial insemination (AI); and Double PRP infusion (D-PRP, n = 21) with the first infusion at 30 h after ovulation induction and the second 4 h after AI. Insemination was performed with frozen donkey semen (1 billion sperm) deposited deeply in the uterine horn immediately after ovulation. Endometrial edema, intrauterine fluid (IUF), uterine vascularization, and endometrial cytology were evaluated pre-AI (TCt) and post-AI (6, 24, and 48 h). Uterine biopsies were taken at T48 for histopathological and collagen evaluation. Peripheral blood samples were collected on D5 for serum progesterone measurement, and pregnancy was evaluated via ultrasonography on D14. Data were analyzed using GLMMs, ANOVA, Friedman, and Kruskal-Wallis tests in SAS and GraphPad Prism, with significance set at p < 0.05. The S-PRP group showed less IUF accumulation than the CTR group at T6. Other parameters showed no significant differences among the groups. Cytology revealed a high percentage of inflammatory cells at T6 in all groups, which decreased in subsequent evaluations. In the CTR group, neutrophil percentages were similar to TCt at T24, while treated groups reached this similarity only by T48. Eosinophil percentages increased over time only in the treated groups. Pregnancy rates showed no differences among the groups (CTR: 0 %, S-PRP: 0 %, D-PRP: 10 %). Results indicate that PRP treatments were ineffective in modulating uterine inflammation and did not enhance pregnancy rates in jennies inseminated with frozen donkey semen.
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Affiliation(s)
| | - Henry David Mogollón García
- Departamento de Genética, Evolução, Microbiologia e Imunologia, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brazil; Laboratório de Biologia Computacional e Sistemas, Institut Pasteur, Universidade de São Paulo, SP, Brazil
| | | | | | | | | | | | | | | | - Gabriella Costa Ribeiro
- Escola de Medicina Veterinária e Zootecnia, Universidade Estadual Paulista, Botucatu, SP, Brazil
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Perumalsamy H, Xiao X, Han HY, Oh JH, Yoon S, Heo MB, Lee TG, Kim HY, Yoon TH. Single-cell RNA sequencing uncovers heterogenous immune cell responses upon exposure to food additive (E171) titanium dioxide. J Nanobiotechnology 2024; 22:765. [PMID: 39696498 DOI: 10.1186/s12951-024-03036-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 11/24/2024] [Indexed: 12/20/2024] Open
Abstract
The prospective use of food additive titanium dioxide (E171 TiO2) in a variety of fields (food, pharmaceutics, and cosmetics) prompts proper cellular cytotoxicity and transcriptomic assessment. Interestingly, smaller-sized E171 TiO2 can translocate in bloodstream and induce a diverse immunological response by activating the immune system, which can be either pro-inflammatory or immune-suppressive. Nevertheless, their cellular or immunologic responses in a heterogeneous population of the immune system following exposure of food additive E171 TiO2 is yet to be elucidated. For this purpose, we have used male Sprague-Dawley rats to deliver E171 TiO2 (5 mg/kg bw per day) via non-invasive intratracheal instillation for 13 weeks. After the 4 weeks recovery period, 3 mL of blood samples from both treated and untreated groups were collected for scRNAseq analysis. Firstly, granulocyte G1 activated innate immune response through the upregulation of genes involved in pro-inflammatory cytokine mediated cytotoxicity. Whereas NK cells resulted in heterogeneity role depending on the subsets where NK1 significantly inhibited cytotoxicity, whereas NK2 and NK3 subsets activated pro-B cell population & inhibited T cell mediated cytotoxicity respectively. While NKT_1 activated innate inflammatory responses which was confirmed by cytotoxic CD8+ T killer cell suppression. Similarly, NKT_2 cells promote inflammatory response by releasing lytic granules and MHC-I complex inhibition to arrest cytotoxic T killer cell responses. Conversely, NKT_3 suppressed inflammatory response by release of anti-inflammatory cytokines suggesting the functional heterogeneity of NKT subset. The formation of MHC-I or MHC-II complexes with T-cell subsets resulted in neither B and T cell dysfunction nor cytotoxic T killer cell inhibition suppressing adaptive immune response. Overall, our research offers an innovative high-dimensional approach to reveal immunological and transcriptomic responses of each cell types at the single cell level in a complex heterogeneous cellular environment by reassuring a precise assessment of immunological response of E171 TiO2.
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Affiliation(s)
- Haribalan Perumalsamy
- Institute for Next Generation Material Design, Hanyang University, Seoul, 04763, Republic of Korea
- Research Institute for Convergence of Basic Science, Hanyang University, Seoul, 04763, South Korea
- Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea
| | - Xiao Xiao
- Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea
| | - Hyoung-Yun Han
- Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Republic of Korea
| | - Jung-Hwa Oh
- Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Republic of Korea
| | - Seokjoo Yoon
- Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Republic of Korea
| | - Min Beom Heo
- Nanosafety Metrology Center, Korea Research Institute of Standards and Science (KRISS), Daejeon, Republic of Korea
| | - Tae Geol Lee
- Nanosafety Metrology Center, Korea Research Institute of Standards and Science (KRISS), Daejeon, Republic of Korea
| | - Hyun-Yi Kim
- Institute for Next Generation Material Design, Hanyang University, Seoul, 04763, Republic of Korea
- Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea
- NGeneS Inc., Gyeonggi-do, 15495, Republic of Korea
| | - Tae-Hyun Yoon
- Institute for Next Generation Material Design, Hanyang University, Seoul, 04763, Republic of Korea.
- Research Institute for Convergence of Basic Science, Hanyang University, Seoul, 04763, South Korea.
- Department of Chemistry, College of Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea.
- Department of Medical and Digital Engineering, Hanyang University, Seoul, 04763, Republic of Korea.
- Yoon Idea Lab. Co. Ltd, Seoul, 04763, Republic of Korea.
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Yue C, Zhou H, Wang X, Yu J, Hu Y, Zhou P, Zhao F, Zeng F, Li G, Li Y, Feng Y, Sun X, Huang S, He M, Wu W, Huang N, Li J. Atopic dermatitis: pathogenesis and therapeutic intervention. MedComm (Beijing) 2024; 5:e70029. [PMID: 39654684 PMCID: PMC11625510 DOI: 10.1002/mco2.70029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 11/11/2024] [Accepted: 11/14/2024] [Indexed: 12/12/2024] Open
Abstract
The skin serves as the first protective barrier for nonspecific immunity and encompasses a vast network of skin-associated immune cells. Atopic dermatitis (AD) is a prevalent inflammatory skin disease that affects individuals of all ages and races, with a complex pathogenesis intricately linked to genetic, environmental factors, skin barrier dysfunction as well as immune dysfunction. Individuals diagnosed with AD frequently exhibit genetic predispositions, characterized by mutations that impact the structural integrity of the skin barrier. This barrier dysfunction leads to the release of alarmins, activating the type 2 immune pathway and recruiting various immune cells to the skin, where they coordinate cutaneous immune responses. In this review, we summarize experimental models of AD and provide an overview of its pathogenesis and the therapeutic interventions. We focus on elucidating the intricate interplay between the immune system of the skin and the complex regulatory mechanisms, as well as commonly used treatments for AD, aiming to systematically understand the cellular and molecular crosstalk in AD-affected skin. Our overarching objective is to provide novel insights and inform potential clinical interventions to reduce the incidence and impact of AD.
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Affiliation(s)
- Chengcheng Yue
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Hong Zhou
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Xiaoyan Wang
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Jiadong Yu
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Yawen Hu
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Pei Zhou
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Fulei Zhao
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Fanlian Zeng
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Guolin Li
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Ya Li
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Yuting Feng
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Xiaochi Sun
- Department of CardiologyWest China HospitalSichuan UniversityChengduSichuanChina
| | - Shishi Huang
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Mingxiang He
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Wenling Wu
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Nongyu Huang
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
| | - Jiong Li
- State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversitySichuan University and Collaborative Innovation Center for BiotherapyChengduSichuanChina
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Wu S, Cai B, Wang T, Cao Z, Peng H, Liu H. Eosinophil extracellular traps in respiratory ailment: Pathogenic mechanisms and clinical translation. World J Otorhinolaryngol Head Neck Surg 2024; 10:213-224. [PMID: 39233861 PMCID: PMC11369806 DOI: 10.1002/wjo2.138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 08/07/2023] [Accepted: 08/10/2023] [Indexed: 09/06/2024] Open
Abstract
Background Eosinophilic extracellular traps (EETs) are reticular complexes comprising deoxyribonucleic-Acid (DNA) fibers and granule proteins. Aims EETs play a crucial role in antimicrobial host responses and are pathogenic when overproduced or under degraded. EETs created by eosinophils appear to enable vital immune responses against extra-cellular pathogens, nevertheless, trap overproduction is evident in pathology. Materials & Methods As considerably research is performed, new data affirmed that EETs can alter the outcome of respiratory ailment. Results We probe into the disclosure and specificity of EETs produced in reaction to various stimuli and propose a role for those frameworks in ailment pathogenesis and the establishment of chronic, unresolved inflammation. Discussion Whether EETs can be used as a prospective brand-new target for the diagnosis, treatment and prognosis of respiratory ailments is a scientific theme worth studying. Conclusion We probe into the disclosure and specificity of EETs produced in reaction to various stimuli and propose a role for those frameworks in ailment pathogenesis and the establishment of chronic, unresolved inflammation.
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Affiliation(s)
- Shun‐Yu Wu
- Department of OtolaryngologyThe Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital)ShanghaiChina
| | - Bo‐Yu Cai
- Department of OtolaryngologyThe Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital)ShanghaiChina
| | - Tian‐Yu Wang
- Department of OtolaryngologyThe Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital)ShanghaiChina
| | - Zhi‐Wen Cao
- Department of OtolaryngologyThe Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital)ShanghaiChina
| | - Hu Peng
- Department of OtolaryngologyThe Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital)ShanghaiChina
| | - Huan‐Hai Liu
- Department of OtolaryngologyThe Second Affiliated Hospital of the Naval Military Medical University (Shanghai Changzheng Hospital)ShanghaiChina
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Ismahil MA, Zhou G, Gao M, Bansal SS, Patel B, Limdi N, Xie M, Antipenko S, Rokosh G, Hamid T, Prabhu SD. Splenic CD169 + Tim4 + Marginal Metallophilic Macrophages Are Essential for Wound Healing After Myocardial Infarction. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.08.09.24311769. [PMID: 39211861 PMCID: PMC11361232 DOI: 10.1101/2024.08.09.24311769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Fidelity of wound healing after myocardial infarction (MI) is an important determinant of subsequent adverse cardiac remodeling and failure. Macrophages derived from infiltrating Ly6C hi blood monocytes are a key component of this healing response; however, the importance of other macrophage populations is unclear. Here, using a variety of in vivo murine models and orthogonal approaches, including surgical myocardial infarction, splenectomy, parabiosis, cell adoptive transfer, lineage tracing and cell tracking, RNA sequencing, and functional characterization, we establish in mice an essential role for splenic CD169 + Tim4 + marginal metallophilic macrophages (MMMs) in post-MI wound healing. Splenic CD169 + Tim4 + MMMs circulate in blood as Ly6C low cells expressing macrophage markers and help populate CD169 + Tim4 + CCR2 - LYVE1 low macrophages in the naïve heart. After acute MI, splenic MMMs augment phagocytosis, CCR3 and CCR4 expression, and robustly mobilize to the heart, resulting in marked expansion of cardiac CD169 + Tim4 + LyVE1 low macrophages with an immunomodulatory and pro-resolving gene signature. These macrophages are obligatory for apoptotic neutrophil clearance, suppression of inflammation, and induction of a reparative macrophage phenotype in the infarcted heart. Splenic MMMs are both necessary and sufficient for post-MI wound healing, and limit late pathological remodeling. Liver X receptor-α agonist-induced expansion of the splenic marginal zone and MMMs during acute MI alleviates inflammation and improves short- and long-term cardiac remodeling. Finally, humans with acute ST-elevation MI also exhibit expansion of circulating CD169 + Tim4 + macrophages. We conclude that splenic CD169 + Tim4 + MMMs are required for pro-resolving and reparative responses after MI and can be manipulated for therapeutic benefit to limit long-term heart failure. CLINICAL PERSPECTIVE What is new?: We establish for the first time that metallophilic marginal macrophages (MMMs) from the spleen, expressing the markers CD169 and Tim4, circulate in blood and traffic to the heart to help maintain the CD169 + Tim4 + CCR2 - LYVE1 low macrophage population in the heart. After acute myocardial infarction, splenic MMMs augment cardiac trafficking in response to chemotactic signals, resulting in expansion of CD169 + Tim4 + macrophages in the heart that play an essential role in post-MI efferocytosis, wound healing and repair while limiting longer term adverse cardiac remodeling. Analogous to mice, humans also exhibit circulating CD169 + Tim4 + macrophages in the blood that expand after acute ST segment elevation MI. What are the clinical implications?: This study highlights the importance of the cardiosplenic axis in acute MI, and the splenic marginal zone, in determining the course and outcome of post-MI LV remodeling.Pharmacological expansion of splenic marginal zone macrophages alleviated post-MI adverse LV remodeling and inflammation, suggesting that splenic modulation is a potential translational therapeutic approach for limiting post-MI inflammation and improving heart repair.
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Sun H, Li S, Wang Q, Luo C, Zhong L, Wan G, Li Z, Zhao G, Bu X, Zeng M, Feng G. Formyl peptide enhances cancer immunotherapy by activating antitumoral neutrophils, and T cells. Biomed Pharmacother 2024; 175:116670. [PMID: 38692065 DOI: 10.1016/j.biopha.2024.116670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 04/17/2024] [Accepted: 04/24/2024] [Indexed: 05/03/2024] Open
Abstract
Neutrophils are heterogeneous and plastic, with the ability to polarize from antitumour to protumour phenotype and modulate tumour microenvironment components. While some advances have been made, the neutrophil-targeting therapy remains underexplored. Activation of formyl peptide receptors (FPRs) by formylated peptides is needed for local control of infection through the recruitment of activated neutrophils while the potential contribution of antitumour activity remains underexplored. Here, we demonstrate that neutrophils can be harnessed to suppress tumour growth through the action of the formyl peptide (FP) on the formyl peptide receptor (FPR). Mechanistically, FP efficiently recruits neutrophils to produce reactive oxygen species production (ROS), resulting in the direct killing of tumours. Antitumour functions disappeared when neutrophils were depleted by anti-Ly6G antibodies. Interestingly, extensive T-cell activation was observed in mouse tumours treated with FP, showing the potential to alter the immune suppressed tumour microenvironment (TME) and further sensitize mice to anti-PD1 therapy. Transcriptomic and flow cytometry analyses revealed the mechanisms of FP-sensitized anti-PD1 therapy, mainly including stimulated neutrophils and an altered immune-suppressed tumour microenvironment. Collectively, these data establish FP as an effective combination partner for sensitizing anti-PD1 therapy by stimulating tumour-infiltrated neutrophils.
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Affiliation(s)
- Haixia Sun
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou,Guangdong 510060, China; Department of Pharmacy, Shenzhen Third People's Hospital, Shenzhen, Guangdong Province 518112, China
| | - Shuxin Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou,Guangdong 510060, China
| | - Qiaoli Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou,Guangdong 510060, China
| | - Chunxiang Luo
- Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-Sen University, Nanning 530022, China
| | - Lanyi Zhong
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou,Guangdong 510060, China
| | - Guohui Wan
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China
| | - Ziqian Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou,Guangdong 510060, China
| | - Gexin Zhao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou,Guangdong 510060, China
| | - Xianzhang Bu
- School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China
| | - Musheng Zeng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou,Guangdong 510060, China
| | - Guokai Feng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou,Guangdong 510060, China.
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10
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Rio P, Gasbarrini A, Gambassi G, Cianci R. Pollutants, microbiota and immune system: frenemies within the gut. Front Public Health 2024; 12:1285186. [PMID: 38799688 PMCID: PMC11116734 DOI: 10.3389/fpubh.2024.1285186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 04/24/2024] [Indexed: 05/29/2024] Open
Abstract
Pollution is a critical concern of modern society for its heterogeneous effects on human health, despite a widespread lack of awareness. Environmental pollutants promote several pathologies through different molecular mechanisms. Pollutants can affect the immune system and related pathways, perturbing its regulation and triggering pro-inflammatory responses. The exposure to several pollutants also leads to alterations in gut microbiota with a decreasing abundance of beneficial microbes, such as short-chain fatty acid-producing bacteria, and an overgrowth of pro-inflammatory species. The subsequent intestinal barrier dysfunction, together with oxidative stress and increased inflammatory responses, plays a role in the pathogenesis of gastrointestinal inflammatory diseases. Moreover, pollutants encourage the inflammation-dysplasia-carcinoma sequence through various mechanisms, such as oxidative stress, dysregulation of cellular signalling pathways, cell cycle impairment and genomic instability. In this narrative review, we will describe the interplay between pollutants, gut microbiota, and the immune system, focusing on their relationship with inflammatory bowel diseases and colorectal cancer. Understanding the biological mechanisms underlying the health-to-disease transition may allow the design of public health policies aimed at reducing the burden of disease related to pollutants.
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Affiliation(s)
| | | | | | - Rossella Cianci
- Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
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11
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Gigon L, Müller P, Haenni B, Iacovache I, Barbo M, Gosheva G, Yousefi S, Soragni A, von Ballmoos C, Zuber B, Simon HU. Membrane damage by MBP-1 is mediated by pore formation and amplified by mtDNA. Cell Rep 2024; 43:114084. [PMID: 38583154 DOI: 10.1016/j.celrep.2024.114084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 12/28/2023] [Accepted: 03/25/2024] [Indexed: 04/09/2024] Open
Abstract
Eosinophils play a crucial role in host defense while also contributing to immunopathology through the release of inflammatory mediators. Characterized by distinctive cytoplasmic granules, eosinophils securely store and rapidly release various proteins exhibiting high toxicity upon extracellular release. Among these, major basic protein 1 (MBP-1) emerges as an important mediator in eosinophil function against pathogens and in eosinophil-associated diseases. While MBP-1 targets both microorganisms and host cells, its precise mechanism remains elusive. We demonstrate that formation of small pores by MBP-1 in lipid bilayers induces membrane permeabilization and disrupts potassium balance. Additionally, we reveal that mitochondrial DNA (mtDNA) present in eosinophil extracellular traps (EETs) amplifies MBP-1 toxic effects, underscoring the pivotal role of mtDNA in EETs. Furthermore, we present evidence indicating that absence of CpG methylation in mtDNA contributes to the regulation of MBP-1-mediated toxicity. Taken together, our data suggest that the mtDNA scaffold within extracellular traps promotes MBP-1 toxicity.
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Affiliation(s)
- Lea Gigon
- Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland
| | - Philipp Müller
- Department of Chemistry, Biochemistry, and Pharmaceutical Sciences, University of Bern, 3012 Bern, Switzerland
| | - Beat Haenni
- Institute of Anatomy, University of Bern, 3012 Bern, Switzerland
| | - Ioan Iacovache
- Institute of Anatomy, University of Bern, 3012 Bern, Switzerland
| | - Maruša Barbo
- Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland; Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Gordana Gosheva
- Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland; Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia
| | - Shida Yousefi
- Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland
| | - Alice Soragni
- Department of Orthopedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Christoph von Ballmoos
- Department of Chemistry, Biochemistry, and Pharmaceutical Sciences, University of Bern, 3012 Bern, Switzerland
| | - Benoît Zuber
- Institute of Anatomy, University of Bern, 3012 Bern, Switzerland
| | - Hans-Uwe Simon
- Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland; Institute of Biochemistry, Brandenburg Medical School, 16816 Neuruppin, Germany.
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12
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Krause C, Bergmann E, Schmidt SV. Epigenetic modulation of myeloid cell functions in HIV and SARS-CoV-2 infection. Mol Biol Rep 2024; 51:342. [PMID: 38400997 PMCID: PMC10894183 DOI: 10.1007/s11033-024-09266-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 01/18/2024] [Indexed: 02/26/2024]
Abstract
Myeloid cells play a vital role in innate immune responses as they recognize and phagocytose pathogens like viruses, present antigens, produce cytokines, recruit other immune cells to combat infections, and contribute to the attenuation of immune responses to restore homeostasis. Signal integration by pathogen recognition receptors enables myeloid cells to adapt their functions by a network of transcription factors and chromatin remodelers. This review provides a brief overview of the subtypes of myeloid cells and the main epigenetic regulation mechanisms. Special focus is placed on the epigenomic alterations in viral nucleic acids of HIV and SARS-CoV-2 along with the epigenetic changes in the host's myeloid cell compartment. These changes are important as they lead to immune suppression and promote the progression of the disease. Finally, we highlight some promising examples of 'epidrugs' that modulate the epigenome of immune cells and could be used as therapeutics for viral infections.
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Affiliation(s)
- Carolyn Krause
- Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 53127, Bonn, Germany
- Department of Microbiology and Immunology, the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, 3000, Australia
| | - Eva Bergmann
- Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 53127, Bonn, Germany
| | - Susanne Viktoria Schmidt
- Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 53127, Bonn, Germany.
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13
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I Kutyavin V, Korn LL, Medzhitov R. Nutrient-derived signals regulate eosinophil adaptation to the small intestine. Proc Natl Acad Sci U S A 2024; 121:e2316446121. [PMID: 38271336 PMCID: PMC10835075 DOI: 10.1073/pnas.2316446121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 12/05/2023] [Indexed: 01/27/2024] Open
Abstract
Eosinophils are well recognized as effector cells of type 2 immunity, yet they also accumulate in many tissues under homeostatic conditions. However, the processes that govern homeostatic eosinophil accumulation and tissue-specific adaptation, and their functional significance, remain poorly defined. Here, we investigated how eosinophils adapt to the small intestine (SI) microenvironment and the local signals that regulate this process. We observed that eosinophils gradually migrate along the crypt-villus axis, giving rise to a villus-resident subpopulation with a distinct transcriptional signature. Retinoic acid signaling was specifically required for maintenance of this subpopulation, while IL-5 was largely dispensable outside of its canonical role in eosinophil production. Surprisingly, we found that a high-protein diet suppressed the accumulation of villus-resident eosinophils. Purified amino acids were sufficient for this effect, which was a consequence of accelerated eosinophil turnover within the tissue microenvironment and was not due to altered development in the bone marrow. Our study provides insight into the process of eosinophil adaptation to the SI, highlighting its reliance on nutrient-derived signals.
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Affiliation(s)
- Vassily I Kutyavin
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510
| | - Lisa L Korn
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510
- Department of Medicine (Rheumatology), Yale University School of Medicine, New Haven, CT 06510
| | - Ruslan Medzhitov
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510
- HHMI, Yale University School of Medicine, New Haven, CT 06510
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14
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Rawat S, Kumar S, Duggal S, Banerjee A. Phenotypic alteration by dengue virus serotype 2 delays neutrophil apoptosis and stimulates the release of prosurvival secretome with immunomodulatory functions. J Leukoc Biol 2024; 115:276-292. [PMID: 37890093 DOI: 10.1093/jleuko/qiad133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 09/29/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
Neutrophils are the most abundant granuloytes, are phenotypically heterogeneous, and exert detrimental or protective roles during antiviral response. Dengue virus has been reported to activate neutrophils. However, the effect of the dengue virus on the neutrophil phenotypes, survival, and release of inflammatory secretome is yet to be understood. Herein, we investigated the effect of dengue virus serotype 2 (DV-2) on effector functions of naïve neutrophils and studied the impact of its secretome on different immune cells. We found that DV-2 activates purified human neutrophils and causes a significant shift toward the CD16bright/CD62Ldim subtype in a multiplicity of infection and time-dependent manner. These phenotypically altered neutrophils show delayed apoptosis through nuclear factor κB and PI3K pathways and have decreased phagocytic capacity. Treatment of neutrophils with myeloperoxidase and PAD4 inhibitor before DV-2 incubation significantly reduced DV-2-induced double-stranded DNA release, suggesting that myeloperoxidase and PAD4 were involved at early stages for the neutrophil activation and double-stranded DNA release. We also report that DV-2-stimulated neutrophil secretome had a significant effect on viral infection, platelet activation, and naïve neutrophil survival via binding of tumor necrosis factor α to tumor necrosis factor receptor 1/2 receptors. Furthermore, incubation of endothelial cells with the DV-2-stimulated neutrophil secretome potentially inhibits proliferation and wound healing capacity and induces endothelial cell death, which can contribute to endothelial barrier dysfunction. In conclusion, the neutrophil-DV-2 interaction modulates the phenotype of neutrophils and the release of prosurvival and antiviral secretome that may act as a double-edged sword during dengue pathogenesis.
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Affiliation(s)
- Surender Rawat
- Laboratory of Virology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurugram Expressway, Faridabad, 121001, Haryana, India
| | - Shubham Kumar
- Laboratory of Virology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurugram Expressway, Faridabad, 121001, Haryana, India
| | - Shweta Duggal
- Laboratory of Virology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurugram Expressway, Faridabad, 121001, Haryana, India
| | - Arup Banerjee
- Laboratory of Virology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurugram Expressway, Faridabad, 121001, Haryana, India
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15
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Xiao Y, Cheng Y, Liu WJ, Liu K, Wang Y, Xu F, Wang DM, Yang Y. Effects of neutrophil fate on inflammation. Inflamm Res 2023; 72:2237-2248. [PMID: 37925664 DOI: 10.1007/s00011-023-01811-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 09/18/2023] [Accepted: 10/24/2023] [Indexed: 11/07/2023] Open
Abstract
INTRODUCTION Neutrophils are important participants in the innate immune response. They rapidly and efficiently identify and clear infectious agents by expressing large numbers of membrane receptors. Upon tissue injury or pathogen invasion, neutrophils are the first immune cells to reach the site of injury and participate in the inflammatory response. MATERIALS AND METHODS A thorough search on PubMed related to neutrophil death or clearance pathways was performed. CONCLUSION Inflammatory response and tissue damage can be aggravated when neutrophils are not removed rapidly from the site of injury. Recent studies have shown that neutrophils can be cleared through a variety of pathways, including non-inflammatory and inflammatory death, as well as reverse migration. Non-inflammatory death pathways include apoptosis and autophagy. Inflammatory death pathways include necroptosis, pyroptosis and NETosis. This review highlights the basic properties of neutrophils and the impact of their clearance pathways on the inflammatory response.
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Affiliation(s)
- Yuan Xiao
- Department of Anesthesiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Yang Cheng
- Department of Anesthesiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Wen-Jie Liu
- Department of Anesthesiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Kun Liu
- Department of Anesthesiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Yan Wang
- Department of Anesthesiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - Feng Xu
- Department of Anesthesiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China
| | - De-Ming Wang
- Department of Anesthesiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China.
| | - Yi Yang
- Department of Anesthesiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China.
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16
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Balkrishna A, Sharma S, Gohel V, Kumari A, Rawat M, Maity M, Sinha S, Dev R, Varshney A. Renogrit attenuates Vancomycin-induced nephrotoxicity in human renal spheroids and in Sprague-Dawley rats by regulating kidney injury biomarkers and creatinine/urea clearance. PLoS One 2023; 18:e0293605. [PMID: 37939153 PMCID: PMC10631690 DOI: 10.1371/journal.pone.0293605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 10/09/2023] [Indexed: 11/10/2023] Open
Abstract
Vancomycin, is widely used against methicillin-resistant bacterial infections. However, Vancomycin accumulation causes nephrotoxicity which leads to an impairment in the filtration mechanisms of kidney. Traditional herbal medicines hold potential for treatment of drug-induced nephrotoxicity. Herein, we investigated protective properties of plant-based medicine Renogrit against Vancomycin-induced kidney injury. Phytometabolite analysis of Renogrit was performed by UHPLC. Spheroids formed from human proximal tubular cell (HK-2) were used for in vitro evaluation of Vancomycin-induced alterations in cell viability, P-gp functionality, NAG, KIM-1 levels, and mRNA expression of NGAL and MMP-7. The in vivo efficacy of Renogrit against Vancomycin-induced nephrotoxicity was further evaluated in Sprague-Dawley (SD) rats by measurement of BUN, serum creatinine, and their respective clearances. Moreover, eGFR, kidney-to-body weight ratio, GSH/GSSG ratio, KIM-1, NAG levels and mRNA expression of KIM-1 and osteopontin were also analyzed. Changes in histopathology of kidney and hematological parameters were also observed. Renogrit treatment led to an increase in cell viability, normalization of P-gp functionality, decrease in levels of NAG, KIM-1, and reduction in mRNA expression of NGAL and MMP-7. In Vancomycin-challenged SD rats, Renogrit treatment normalized altered kidney functions, histological, and hematological parameters. Our findings revealed that Renogrit holds a clinico-therapeutic potential for alleviating Vancomycin-associated nephrotoxicity.
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Affiliation(s)
- Acharya Balkrishna
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, Uttarakhand, India
- Department of Allied and Applied Sciences, University of Patanjali, Haridwar, Uttarakhand, India
- Patanjali Yog Peeth (UK) Trust, Glasgow, United Kingdom
| | - Sonam Sharma
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, Uttarakhand, India
| | - Vivek Gohel
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, Uttarakhand, India
| | - Ankita Kumari
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, Uttarakhand, India
| | - Malini Rawat
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, Uttarakhand, India
| | - Madhulina Maity
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, Uttarakhand, India
| | - Sandeep Sinha
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, Uttarakhand, India
| | - Rishabh Dev
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, Uttarakhand, India
| | - Anurag Varshney
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, Uttarakhand, India
- Department of Allied and Applied Sciences, University of Patanjali, Haridwar, Uttarakhand, India
- Special Centre for Systems Medicine, Jawaharlal Nehru University, New Delhi, India
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17
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Gigon L, Fettrelet T, Miholic M, McLeish KR, Yousefi S, Stojkov D, Simon HU. Syntaxin-4 and SNAP23 are involved in neutrophil degranulation, but not in the release of mitochondrial DNA during NET formation. Front Immunol 2023; 14:1272699. [PMID: 37885878 PMCID: PMC10599146 DOI: 10.3389/fimmu.2023.1272699] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 09/26/2023] [Indexed: 10/28/2023] Open
Abstract
Neutrophils are a specialized subset of white blood cells, which have the ability to store pre-formed mediators in their cytoplasmic granules. Neutrophils are well-known effector cells involved in host protection against pathogens through diverse mechanisms such as phagocytosis, degranulation, extracellular traps, and oxidative burst. In this study, we provide evidence highlighting the significance of the SNARE proteins syntaxin-4 and synaptosomal-associated protein (SNAP) 23 in the release of azurophilic granules, specific granules, and the production of reactive oxygen species in human neutrophils. In contrast, the specific blockade of either syntaxin-4 or SNAP23 did not prevent the release of mitochondrial dsDNA in the process of neutrophil extracellular trap (NET) formation. These findings imply that degranulation and the release of mitochondrial dsDNA involve at least partially distinct molecular pathways in neutrophils.
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Affiliation(s)
- Lea Gigon
- Institute of Pharmacology, University of Bern, Bern, Switzerland
| | | | - Marta Miholic
- Institute of Pharmacology, University of Bern, Bern, Switzerland
- Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
| | - Kenneth R. McLeish
- Department of Medicine, University of Louisville School of Medicine, Louisville, KY, United States
| | - Shida Yousefi
- Institute of Pharmacology, University of Bern, Bern, Switzerland
| | - Darko Stojkov
- Institute of Pharmacology, University of Bern, Bern, Switzerland
| | - Hans-Uwe Simon
- Institute of Pharmacology, University of Bern, Bern, Switzerland
- Institute of Biochemistry, Brandenburg Medical School, Neuruppin, Germany
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18
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Swapna LS, Huang M, Li Y. GTM-decon: guided-topic modeling of single-cell transcriptomes enables sub-cell-type and disease-subtype deconvolution of bulk transcriptomes. Genome Biol 2023; 24:190. [PMID: 37596691 PMCID: PMC10436670 DOI: 10.1186/s13059-023-03034-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 08/09/2023] [Indexed: 08/20/2023] Open
Abstract
Cell-type composition is an important indicator of health. We present Guided Topic Model for deconvolution (GTM-decon) to automatically infer cell-type-specific gene topic distributions from single-cell RNA-seq data for deconvolving bulk transcriptomes. GTM-decon performs competitively on deconvolving simulated and real bulk data compared with the state-of-the-art methods. Moreover, as demonstrated in deconvolving disease transcriptomes, GTM-decon can infer multiple cell-type-specific gene topic distributions per cell type, which captures sub-cell-type variations. GTM-decon can also use phenotype labels from single-cell or bulk data to infer phenotype-specific gene distributions. In a nested-guided design, GTM-decon identified cell-type-specific differentially expressed genes from bulk breast cancer transcriptomes.
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Affiliation(s)
| | - Michael Huang
- School of Computer Science, McGill University, Montreal, QC, Canada
| | - Yue Li
- School of Computer Science, McGill University, Montreal, QC, Canada.
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19
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Mposhi A, Turner JD. How can early life adversity still exert an effect decades later? A question of timing, tissues and mechanisms. Front Immunol 2023; 14:1215544. [PMID: 37457711 PMCID: PMC10348484 DOI: 10.3389/fimmu.2023.1215544] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 06/14/2023] [Indexed: 07/18/2023] Open
Abstract
Exposure to any number of stressors during the first 1000 days from conception to age 2 years is important in shaping an individual's life trajectory of health and disease. Despite the expanding range of stressors as well as later-life phenotypes and outcomes, the underlying molecular mechanisms remain unclear. Our previous data strongly suggests that early-life exposure to a stressor reduces the capacity of the immune system to generate subsequent generations of naïve cells, while others have shown that, early life stress impairs the capacity of neuronal stem cells to proliferate as they age. This leads us to the "stem cell hypothesis" whereby exposure to adversity during a sensitive period acts through a common mechanism in all the cell types by programming the tissue resident progenitor cells. Furthermore, we review the mechanistic differences observed in fully differentiated cells and suggest that early life adversity (ELA) may alter mitochondria in stem cells. This may consequently alter the destiny of these cells, producing the lifelong "supply" of functionally altered fully differentiated cells.
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20
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Van Pee T, Nawrot TS, van Leeuwen R, Hogervorst J. Ambient particulate air pollution and the intestinal microbiome; a systematic review of epidemiological, in vivo and, in vitro studies. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 878:162769. [PMID: 36907413 DOI: 10.1016/j.scitotenv.2023.162769] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 02/13/2023] [Accepted: 03/06/2023] [Indexed: 05/13/2023]
Abstract
A healthy indigenous intestinal microbiome is indispensable for intra- and extra-intestinal human health. Since well-established factors such as diet and antibiotic use only explain 16 % of the inter-individual variation in gut microbiome composition, recent studies have focused on the association between ambient particulate air pollution and the intestinal microbiome. We systematically summarize and discuss all evidence concerning the effect of particulate air pollution on intestinal bacterial diversity indices, specific bacterial taxa, and potential underlying intestinal mechanisms. To this end, all possibly relevant publications published between February 1982 and January 2023 were screened, and eventually, 48 articles were included. The vast majority (n = 35) of these studies were animal studies. The exposure periods investigated in the human epidemiological studies (n = 12) ranged from infancy through elderly. This systematic review found that intestinal microbiome diversity indices were generally negatively associated with particulate air pollution in epidemiological studies, with an increase in taxa belonging to Bacteroidetes (two studies), Deferribacterota (one study), and Proteobacteria (four studies), a decrease in taxa belonging to Verrucomicrobiota (one study), and no consensus for taxa belonging to Actinobacteria (six studies) and Firmicutes (seven studies). There was no unequivocal effect of ambient particulate air pollution exposure on bacterial indices and taxa in animal studies. Only one study in humans examined a possible underlying mechanism; yet, the included in vitro and animal studies depicted higher gut damage, inflammation, oxidative stress, and permeability in exposed versus unexposed animals. Overall, the population-based studies showed a dose-related continuum of short- and long-term ambient particulate air pollution exposure on lower gut diversity and shifts in taxa over the entire life course.
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Affiliation(s)
- Thessa Van Pee
- Centre for Environmental Sciences, Hasselt University, Agoralaan Building D, 3590 Diepenbeek, Belgium
| | - Tim S Nawrot
- Centre for Environmental Sciences, Hasselt University, Agoralaan Building D, 3590 Diepenbeek, Belgium; Department of Public Health and Primary Care, Leuven University, Herestraat 49-box 706, 3000 Leuven, Belgium.
| | - Romy van Leeuwen
- Centre for Environmental Sciences, Hasselt University, Agoralaan Building D, 3590 Diepenbeek, Belgium
| | - Janneke Hogervorst
- Centre for Environmental Sciences, Hasselt University, Agoralaan Building D, 3590 Diepenbeek, Belgium
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21
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Silva MB, Pinto LDLDS, Medeiros LH, Souza AA, Chavante SF, Filgueira LGA, Camara RBG, Sassaki GL, Rocha HAO, Andrade GPV. Chondroitin Sulfate from Oreochromis niloticus Waste Reduces Leukocyte Influx in an Acute Peritonitis Model. Molecules 2023; 28:molecules28073082. [PMID: 37049845 PMCID: PMC10096408 DOI: 10.3390/molecules28073082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/26/2023] [Accepted: 03/28/2023] [Indexed: 04/14/2023] Open
Abstract
Oreochromis niloticus (tilapia) is one of the most cultivated fish species worldwide. Tilapia farming generates organic waste from fish removal processes in nurseries. Visceral waste can damage natural ecosystems. Therefore, the use of this material as a source of biomolecules helps reduce environmental impacts and improve pharmacological studies. Tilapia viscera were subjected to proteolysis and complexation with an ion-exchange resin. The obtained glycosaminoglycans were purified using ion exchange chromatography (DEAE-Sephacel). The electrophoretic profile and analysis of 1H/13C nuclear magnetic resonance (NMR) spectra allowed for the characterization of the compound as chondroitin sulfate and its sulfation position. This chondroitin was named CST. We tested the ability of CST to reduce leukocyte influx in acute peritonitis models induced by sodium thioglycolate and found a significant reduction in leukocyte migration to the peritoneal cavity, similar to the polymorphonuclear population of the three tested doses of CST. This study shows, for the first time, the potential of CST obtained from O. niloticus waste as an anti-inflammatory drug, thereby contributing to the expansion of the study of molecules with pharmacological functions.
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Affiliation(s)
- Marianna Barros Silva
- Laboratório de Biotecnologia de Polímeros Naturais (BIOPOL), Departamento de Bioquímica, Centro de Biociências, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59078-970, RN, Brazil
| | - Lívia de Lourdes de Sousa Pinto
- Departamento de Bioquímica, Centro de Biociências, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59078-970, RN, Brazil
| | - Luiz Henrique Medeiros
- Departamento de Bioquímica, Centro de Biociências, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59078-970, RN, Brazil
| | - Airton Araújo Souza
- Instituto Federal de Educação, Ciência e Tecnologia do Rio Grande do Norte, Campus de Parnamirim, Parnamirim 59143-455, RN, Brazil
| | - Suely Ferreira Chavante
- Departamento de Bioquímica, Centro de Biociências, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59078-970, RN, Brazil
| | - Luciana Guimarães Alves Filgueira
- Laboratório de Biotecnologia de Polímeros Naturais (BIOPOL), Departamento de Bioquímica, Centro de Biociências, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59078-970, RN, Brazil
| | - Rafael Barros Gomes Camara
- Laboratório de Biotecnologia de Polímeros Naturais (BIOPOL), Departamento de Bioquímica, Centro de Biociências, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59078-970, RN, Brazil
| | - Guilherme Lanzi Sassaki
- Departamento de Bioquímica e Biologia Molecular, Setor de Ciências Biológicas, Universidade Federal do Parana (UFPR), Curitiba 81531-980, PR, Brazil
| | - Hugo Alexandre Oliveira Rocha
- Laboratório de Biotecnologia de Polímeros Naturais (BIOPOL), Departamento de Bioquímica, Centro de Biociências, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59078-970, RN, Brazil
| | - Giulianna Paiva Viana Andrade
- Departamento de Bioquímica, Centro de Biociências, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59078-970, RN, Brazil
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22
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Hanč P, Messou MA, Wang Y, von Andrian UH. Control of myeloid cell functions by nociceptors. Front Immunol 2023; 14:1127571. [PMID: 37006298 PMCID: PMC10064072 DOI: 10.3389/fimmu.2023.1127571] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 02/23/2023] [Indexed: 03/19/2023] Open
Abstract
The immune system has evolved to protect the host from infectious agents, parasites, and tumor growth, and to ensure the maintenance of homeostasis. Similarly, the primary function of the somatosensory branch of the peripheral nervous system is to collect and interpret sensory information about the environment, allowing the organism to react to or avoid situations that could otherwise have deleterious effects. Consequently, a teleological argument can be made that it is of advantage for the two systems to cooperate and form an “integrated defense system” that benefits from the unique strengths of both subsystems. Indeed, nociceptors, sensory neurons that detect noxious stimuli and elicit the sensation of pain or itch, exhibit potent immunomodulatory capabilities. Depending on the context and the cellular identity of their communication partners, nociceptors can play both pro- or anti-inflammatory roles, promote tissue repair or aggravate inflammatory damage, improve resistance to pathogens or impair their clearance. In light of such variability, it is not surprising that the full extent of interactions between nociceptors and the immune system remains to be established. Nonetheless, the field of peripheral neuroimmunology is advancing at a rapid pace, and general rules that appear to govern the outcomes of such neuroimmune interactions are beginning to emerge. Thus, in this review, we summarize our current understanding of the interaction between nociceptors and, specifically, the myeloid cells of the innate immune system, while pointing out some of the outstanding questions and unresolved controversies in the field. We focus on such interactions within the densely innervated barrier tissues, which can serve as points of entry for infectious agents and, where known, highlight the molecular mechanisms underlying these interactions.
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Affiliation(s)
- Pavel Hanč
- Department of Immunology, Harvard Medical School, Boston, MA, United States
- The Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States
- *Correspondence: Pavel Hanč, ; Ulrich H. von Andrian,
| | - Marie-Angèle Messou
- Department of Immunology, Harvard Medical School, Boston, MA, United States
- The Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States
| | - Yidi Wang
- Department of Immunology, Harvard Medical School, Boston, MA, United States
- The Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States
| | - Ulrich H. von Andrian
- Department of Immunology, Harvard Medical School, Boston, MA, United States
- The Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States
- *Correspondence: Pavel Hanč, ; Ulrich H. von Andrian,
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23
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Adrover JM, McDowell SAC, He XY, Quail DF, Egeblad M. NETworking with cancer: The bidirectional interplay between cancer and neutrophil extracellular traps. Cancer Cell 2023; 41:505-526. [PMID: 36827980 DOI: 10.1016/j.ccell.2023.02.001] [Citation(s) in RCA: 106] [Impact Index Per Article: 53.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 01/09/2023] [Accepted: 02/01/2023] [Indexed: 02/25/2023]
Abstract
Neutrophils are major effectors and regulators of the immune system. They play critical roles not only in the eradication of pathogens but also in cancer initiation and progression. Conversely, the presence of cancer affects neutrophil activity, maturation, and lifespan. By promoting or repressing key neutrophil functions, cancer cells co-opt neutrophil biology to their advantage. This co-opting includes hijacking one of neutrophils' most striking pathogen defense mechanisms: the formation of neutrophil extracellular traps (NETs). NETs are web-like filamentous extracellular structures of DNA, histones, and cytotoxic granule-derived proteins. Here, we discuss the bidirectional interplay by which cancer stimulates NET formation, and NETs in turn support disease progression. We review how vascular dysfunction and thrombosis caused by neutrophils and NETs underlie an elevated risk of death from cardiovascular events in cancer patients. Finally, we propose therapeutic strategies that may be effective in targeting NETs in the clinical setting.
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Affiliation(s)
- Jose M Adrover
- Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
| | - Sheri A C McDowell
- Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada; Department of Physiology, Faculty of Medicine, McGill University, Montreal, QC, Canada
| | - Xue-Yan He
- Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
| | - Daniela F Quail
- Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada; Department of Physiology, Faculty of Medicine, McGill University, Montreal, QC, Canada.
| | - Mikala Egeblad
- Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
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24
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Neutrophil extracellular traps as a unique target in the treatment of chemotherapy-induced peripheral neuropathy. EBioMedicine 2023; 90:104499. [PMID: 36870200 PMCID: PMC10009451 DOI: 10.1016/j.ebiom.2023.104499] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 02/09/2023] [Accepted: 02/10/2023] [Indexed: 03/06/2023] Open
Abstract
BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting side effect of chemotherapy and remains a huge clinical challenge. Here, we explore the role of microcirculation hypoxia induced by neutrophil extracellular traps (NETs) in the development of CIPN and look for potential treatment. METHODS The expression of NETs in plasma and dorsal root ganglion (DRG) are examined by ELISA, IHC, IF and Western blotting. IVIS Spectrum imaging and Laser Doppler Flow Metry are applied to explore the microcirculation hypoxia induced by NETs in the development of CIPN. Stroke Homing peptide (SHp)-guided deoxyribonuclease 1 (DNase1) is used to degrade NETs. FINDINGS The level of NETs in patients received chemotherapy increases significantly. And NETs accumulate in the DRG and limbs in CIPN mice. It leads to disturbed microcirculation and ischemic status in limbs and sciatic nerves treated with oxaliplatin (L-OHP). Furthermore, targeting NETs with DNase1 significantly reduces the chemotherapy-induced mechanical hyperalgesia. The pharmacological or genetic inhibition on myeloperoxidase (MPO) or peptidyl arginine deiminase-4 (PAD4) dramatically improves microcirculation disturbance caused by L-OHP and prevents the development of CIPN in mice. INTERPRETATION In addition to uncovering the role of NETs as a key element in the development of CIPN, our finding provides a potential therapeutic strategy that targeted degradation of NETs by SHp-guided DNase1 could be an effective treatment for CIPN. FUNDING This study was funded by the National Natural Science Foundation of China81870870, 81971047, 81773798, 82271252; Natural Science Foundation of Jiangsu ProvinceBK20191253; Major Project of "Science and Technology Innovation Fund" of Nanjing Medical University2017NJMUCX004; Key R&D Program (Social Development) Project of Jiangsu ProvinceBE2019732; Nanjing Special Fund for Health Science and Technology DevelopmentYKK19170.
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25
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Abstract
Neutrophils or polymorphonuclear neutrophils (PMNs) are an important component of innate host defense. These phagocytic leukocytes are recruited to infected tissues and kill invading microbes. There are several general characteristics of neutrophils that make them highly effective as antimicrobial cells. First, there is tremendous daily production and turnover of granulocytes in healthy adults-typically 1011 per day. The vast majority (~95%) of these cells are neutrophils. In addition, neutrophils are mobilized rapidly in response to chemotactic factors and are among the first leukocytes recruited to infected tissues. Most notably, neutrophils contain and/or produce an abundance of antimicrobial molecules. Many of these antimicrobial molecules are toxic to host cells and can destroy host tissues. Thus, neutrophil activation and turnover are highly regulated processes. To that end, aged neutrophils undergo apoptosis constitutively, a process that contains antimicrobial function and proinflammatory capacity. Importantly, apoptosis facilitates nonphlogistic turnover of neutrophils and removal by macrophages. This homeostatic process is altered by interaction with microbes and their products, as well as host proinflammatory molecules. Microbial pathogens can delay neutrophil apoptosis, accelerate apoptosis following phagocytosis, or cause neutrophil cytolysis. Here, we review these processes and provide perspective on recent studies that have potential to impact this paradigm.
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Affiliation(s)
- Scott D Kobayashi
- Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
| | - Frank R DeLeo
- Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
| | - Mark T Quinn
- Department of Microbiology & Cell Biology, Montana State University, Bozeman, Montana, USA
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26
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Motta G, Gualtieri M, Saibene M, Bengalli R, Brigliadori A, Carrière M, Mantecca P. Preliminary Toxicological Analysis in a Safe-by-Design and Adverse Outcome Pathway-Driven Approach on Different Silver Nanoparticles: Assessment of Acute Responses in A549 Cells. TOXICS 2023; 11:toxics11020195. [PMID: 36851069 PMCID: PMC9965967 DOI: 10.3390/toxics11020195] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 02/08/2023] [Accepted: 02/10/2023] [Indexed: 05/15/2023]
Abstract
Silver nanoparticles (Ag NPs) are among the most widely used metal-based nanomaterials (NMs) and their applications in different products, also as antibacterial additives, are increasing. In the present manuscript, according to an adverse outcome pathway (AOP) approach, we tested two safe-by-design (SbD) newly developed Ag NPs coated with hydroxyethyl cellulose (HEC), namely AgHEC powder and AgHEC solution. These novel Ag NPs were compared to two reference Ag NPs (naked and coated with polyvinylpyrrolidone-PVP). Cell viability, inflammatory response, reactive oxygen species, oxidative DNA damage, cell cycle, and cell-particle interactions were analyzed in the alveolar in vitro model, A549 cells. The results show a different toxicity pattern of the novel Ag NPs compared to reference NPs and that between the two novel NPs, the AgHEC solution is the one with the lower toxicity and to be further developed within the SbD framework.
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Affiliation(s)
- Giulia Motta
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy
- Research Centre POLARIS, Department of Earth and Environmental Sciences, University of Milano-Bicocca, 20126 Milan, Italy
| | - Maurizio Gualtieri
- Research Centre POLARIS, Department of Earth and Environmental Sciences, University of Milano-Bicocca, 20126 Milan, Italy
- Department of Earth and Environmental Sciences, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milan, Italy
- Correspondence: ; Tel.: +39-026-448-2110
| | - Melissa Saibene
- Research Centre POLARIS, Department of Earth and Environmental Sciences, University of Milano-Bicocca, 20126 Milan, Italy
- Department of Earth and Environmental Sciences, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milan, Italy
| | - Rossella Bengalli
- Research Centre POLARIS, Department of Earth and Environmental Sciences, University of Milano-Bicocca, 20126 Milan, Italy
- Department of Earth and Environmental Sciences, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milan, Italy
| | - Andrea Brigliadori
- National Research Council of Italy, Institute of Science, Technology and Sustainability for Ceramics (CNR-ISSMC former CNR-ISTEC), Via Granarolo 64, 48018 Faenza, Italy
| | - Marie Carrière
- Univ. Grenoble-Alpes, CEA, CNRS, IRIG, SyMMES, CIBEST, 38000 Grenoble, France
| | - Paride Mantecca
- Research Centre POLARIS, Department of Earth and Environmental Sciences, University of Milano-Bicocca, 20126 Milan, Italy
- Department of Earth and Environmental Sciences, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milan, Italy
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Abstract
PURPOSE OF REVIEW Over the last years, extensive research has been done on neutrophils and their contribution in chronic rhinosinusitis (CRS), and made it clear that they are more than just a bystander in this disease. In this article, we will review all recent publications on this topic and look to what the future hold regarding therapeutics targeting the neutrophilic inflammation in CRS. RECENT FINDINGS Evidence is growing that the presence of neutrophils are associated with a worse disease outcome in certain CRS patient groups. They are highly activated in type 2 inflammations and exhibit damaging properties through their proteases, contributing to the chronicity of the disease. Several recent studies identified useful biomarkers and targets for future therapeutics. SUMMARY The findings we review in this manuscript are of utmost importance in unraveling the complexity of CRS and provide us with the necessary knowledge for future clinical practices.
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Affiliation(s)
- Tim Delemarre
- Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium
| | - Claus Bachert
- Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium
- Division of ENT Diseases, CLINTEC, Karolinska Institute, Stockholm, Sweden
- First Affiliated Hospital, Sun Yat-Sen University, International Airway Research Center, Guangzhou, China
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28
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Kaufmann T, Simon HU. Pharmacological Induction of Granulocyte Cell Death as Therapeutic Strategy. Annu Rev Pharmacol Toxicol 2023; 63:231-247. [PMID: 36028226 DOI: 10.1146/annurev-pharmtox-051921-115130] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Apoptosis is central for the maintenance of health. In the immune system, apoptosis guarantees proper development of immune cells and shutdown of immune reactions by the coordinated elimination of activated immune cells. Limitation of the life span of granulocytes is important, as overactivation of these cells is associated with chronic inflammation and collateral tissue damage. Consequently, targeted induction of granulocyte apoptosis may be beneficial in the course of respective immune disorders. Anti-inflammatory drugs such as glucocorticoids and monoclonal antibodies against IL-5Rα exert their function in part by triggering eosinophil apoptosis. Agonistic antibodies targeting Siglec-8 or death receptors are tested (pre)clinically. Moreover, a new class of inhibitors targeting antiapoptotic BCL-2 proteins shows great promise for anticancer treatments. Because of their specificity and tolerable side effects, these so-called BH3 mimetics may be worthwhile to evaluate in inflammatory disorders. Here, we review past and recent data on pharmacological apoptosis induction of granulocytes and highlight respective therapeutic potential.
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Affiliation(s)
- Thomas Kaufmann
- Institute of Pharmacology, University of Bern, Bern, Switzerland; ,
| | - Hans-Uwe Simon
- Institute of Pharmacology, University of Bern, Bern, Switzerland; , .,Department of Clinical Immunology and Allergology, Sechenov University, Moscow, Russia.,Laboratory of Molecular Immunology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.,Brandenburg Medical School, Neuruppin, Germany
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29
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Christenson JL, Williams MM, Richer JK. The underappreciated role of resident epithelial cell populations in metastatic progression: contributions of the lung alveolar epithelium. Am J Physiol Cell Physiol 2022; 323:C1777-C1790. [PMID: 36252127 PMCID: PMC9744653 DOI: 10.1152/ajpcell.00181.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 10/17/2022] [Accepted: 10/17/2022] [Indexed: 12/14/2022]
Abstract
Metastatic cancer is difficult to treat and is responsible for the majority of cancer-related deaths. After cancer cells initiate metastasis and successfully seed a distant site, resident cells in the tissue play a key role in determining how metastatic progression develops. The lung is the second most frequent site of metastatic spread, and the primary site of metastasis within the lung is alveoli. The most abundant cell type in the alveolar niche is the epithelium. This review will examine the potential contributions of the alveolar epithelium to metastatic progression. It will also provide insight into other ways in which alveolar epithelial cells, acting as immune sentinels within the lung, may influence metastatic progression through their various interactions with cells in the surrounding microenvironment.
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Affiliation(s)
- Jessica L Christenson
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Michelle M Williams
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Jennifer K Richer
- Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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30
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Pan G, Zhang P, Yang J, Wu Y. The regulatory effect of specialized pro-resolving mediators on immune cells. Biomed Pharmacother 2022; 156:113980. [DOI: 10.1016/j.biopha.2022.113980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 10/22/2022] [Accepted: 11/04/2022] [Indexed: 11/08/2022] Open
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Özcan A, Boyman O. Mechanisms regulating neutrophil responses in immunity, allergy, and autoimmunity. Allergy 2022; 77:3567-3583. [PMID: 36067034 PMCID: PMC10087481 DOI: 10.1111/all.15505] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 08/16/2022] [Accepted: 09/03/2022] [Indexed: 01/28/2023]
Abstract
Neutrophil granulocytes, or neutrophils, are the most abundant circulating leukocytes in humans and indispensable for antimicrobial immunity, as exemplified in patients with inborn and acquired defects of neutrophils. Neutrophils were long regarded as the foot soldiers of the immune system, solely destined to execute a set of effector functions against invading pathogens before undergoing apoptosis, the latter of which was ascribed to their short life span. This simplistic understanding of neutrophils has now been revised on the basis of insights gained from the use of mouse models and single-cell high-throughput techniques, revealing tissue- and context-specific roles of neutrophils in guiding immune responses. These studies also demonstrated that neutrophil responses were controlled by sophisticated feedback mechanisms, including directed chemotaxis of neutrophils to tissue-draining lymph nodes resulting in modulation of antimicrobial immunity and inflammation. Moreover, findings in mice and humans showed that neutrophil responses adapted to different deterministic cytokine signals, which controlled their migration and effector function as well as, notably, their biologic clock by affecting the kinetics of their aging. These mechanistic insights have important implications for health and disease in humans, particularly, in allergic diseases, such as atopic dermatitis and allergic asthma bronchiale, as well as in autoinflammatory and autoimmune diseases. Hence, our improved understanding of neutrophils sheds light on novel therapeutic avenues, focusing on molecularly defined biologic agents.
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Affiliation(s)
- Alaz Özcan
- Department of Immunology, University Hospital Zurich, Zurich, Switzerland
| | - Onur Boyman
- Department of Immunology, University Hospital Zurich, Zurich, Switzerland.,Faculty of Medicine, University of Zurich, Zurich, Switzerland.,Faculty of Science, University of Zurich, Zurich, Switzerland
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Indicators of oxidative stress in leukocytes isolated from bottlenose dolphins (Tursiops truncatus) in response to a proinflammatory challenge. Microb Pathog 2022; 173:105800. [DOI: 10.1016/j.micpath.2022.105800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 09/20/2022] [Accepted: 09/21/2022] [Indexed: 11/06/2022]
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Zhao B, Yin Q, Fei Y, Zhu J, Qiu Y, Fang W, Li Y. Research progress of mechanisms for tight junction damage on blood-brain barrier inflammation. Arch Physiol Biochem 2022; 128:1579-1590. [PMID: 32608276 DOI: 10.1080/13813455.2020.1784952] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Inflammation in the central nervous system (CNS) contributes to disease pathologies by disrupting the integrity of the blood-brain barrier (BBB). Tight junctions (TJ) are a key component of the BBB. Following hypoxic-ischaemic or mechanical injury to the brain, inflammatory mediators are released such as cytokines, chemokines, and growth factors. Simultaneously, matrix metalloproteinases (MMPs) are released which can degrade TJ proteins. Subsequently, the function and morphology of the BBB are disrupted, which allows immune cells an opportunity to enter into the brain parenchyma. This review summarises the information on the role of TJ protein families in the BBB and provides a comprehensive summary of the mechanisms whereby inflammation breaks down the BBB by increasing degradation of TJ proteins.
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Affiliation(s)
- Bo Zhao
- State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Qiyang Yin
- State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Yuxiang Fei
- State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Jianping Zhu
- State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Yanying Qiu
- State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Weirong Fang
- State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Yunman Li
- State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China
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RNA modifications: importance in immune cell biology and related diseases. Signal Transduct Target Ther 2022; 7:334. [PMID: 36138023 PMCID: PMC9499983 DOI: 10.1038/s41392-022-01175-9] [Citation(s) in RCA: 177] [Impact Index Per Article: 59.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 08/23/2022] [Accepted: 08/31/2022] [Indexed: 11/16/2022] Open
Abstract
RNA modifications have become hot topics recently. By influencing RNA processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune cell abnormality in human diseases is also a research focus and progressing rapidly these years. Studies have demonstrated that RNA modifications participate in the multiple biological processes of immune cells, including development, differentiation, activation, migration, and polarization, thereby modulating the immune responses and are involved in some immune related diseases. In this review, we present existing knowledge of the biological functions and underlying mechanisms of RNA modifications, including N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, and adenosine-to-inosine (A-to-I) RNA editing, and summarize their critical roles in immune cell biology. Via regulating the biological processes of immune cells, RNA modifications can participate in the pathogenesis of immune related diseases, such as cancers, infection, inflammatory and autoimmune diseases. We further highlight the challenges and future directions based on the existing knowledge. All in all, this review will provide helpful knowledge as well as novel ideas for the researchers in this area.
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Hu H, Han Y, Cao C, He Y. The triglyceride glucose-body mass index: a non-invasive index that identifies non-alcoholic fatty liver disease in the general Japanese population. J Transl Med 2022; 20:398. [PMID: 36064712 PMCID: PMC9446832 DOI: 10.1186/s12967-022-03611-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 08/24/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND By identifying individuals at high risk for non-alcoholic fatty liver disease (NAFLD), interventional programs could be targeted more effectively. Some studies have demonstrated that triglyceride glucose-body mass index (TyG-BMI) showed an independent positive association with NAFLD. However, research on its diagnostic value in patients with suspected NAFLD is limited. In this study, we aimed to evaluate whether TyG-BMI was accurate in detecting NAFLD in the general Japanese population. METHODS A cross-sectional study of 14,280 individuals who underwent a comprehensive health examination was conducted. Standard protocols were followed to collect anthropometric measurements, lab data, and ultrasonography features. All participants were randomly stratified into the development group (n = 7118) and validation group (n = 7162). The TyG-BMI was calculated. Following this, the diagnostic value of the TyG-BMI was evaluated based on the area under the receiver-operating characteristic curve (AUROC). Two cutoff points were selected and used to rule out or rule in the NALFD, and the specificity, sensitivity, negative predictive value, and positive predictive value were explored, respectively. In order to verify the stability of the results, external verification was performed. RESULTS There were 1272 and 1243 NAFLD participants in the development and validation groups, respectively. The area under the ROC curve (AUC) of TyG-BMI was 0.888 (95% CI 0.876-0.896) and 0.884 (95% CI 0.875-0.894) for the training and validation group, respectively. Using the low TyG-BMI (182.2) cutoff, NAFLD could be excluded with high accuracy (negative predictive value: 96.9% in estimation and 96.9% in validation). The presence of NAFLD could effectively be determined by applying the high cutoff of TyG-BMI (224.0), as the positive predictive value of the estimation and validation groups is 70.7% and 70.1%, respectively. As a result of applying this model, 9996 (70%) of the 14,280 participants would not have undergone ultrasonography, with an accurate prediction of 9308 (93.1%). AUC was 0.874 for external validation using 183,730 Chinese non-obese participants. TyG-BMI was demonstrated to be an excellent diagnostic tool by both internal and external validation. CONCLUSIONS In conclusion, the present study developed and validated a simple, non-invasive, and cost-effective tool to accurately separate participants with and without NAFLD in the Japanese population, rendering ultrasonography for identifying NAFLD unnecessary in a substantial proportion of people.
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Affiliation(s)
- Haofei Hu
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518000, Guangdong, China
- Department of Nephrology, Shenzhen Second People's Hospital, Shenzhen, 518000, Guangdong, China
- Shenzhen University Health Science Center, Shenzhen, 518071, Guangdong, China
| | - Yong Han
- Department of Emergency, Shenzhen Second People's Hospital, Shenzhen, 518000, Guangdong, China
- Department of Emergency, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518000, Guangdong, China
- Shenzhen University Health Science Center, Shenzhen, 518071, Guangdong, China
| | - Changchun Cao
- Department of Rehabilitation, Shenzhen Dapeng New District Nan'ao People's Hospital, No. 6, Renmin Road, Dapeng New District, Shenzhen, 518000, Guangdong, China.
| | - Yongcheng He
- Department of Nephrology, Shenzhen Hengsheng Hospital, No. 20 Yintian Road, Baoan District, Shenzhen, 518000, Guangdong, China.
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Tan JT, Tseng CW. Strongyloides stercoralis hyperinfection presenting with shock and intermittent eosinophilia: A case report. Medicine (Baltimore) 2022; 101:e30490. [PMID: 36107578 PMCID: PMC9439756 DOI: 10.1097/md.0000000000030490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
RATIONALE Strongyloidiasis is a parasitic disease caused by Strongyloides stercoralis. The clinical presentation varies according to the stage of infection. Diagnosing strongyloidiasis is a challenge in clinical practice due to the inconsistency of eosinophilia and the low sensitivity of standard microscopic stool examination. Strongyloides infection presenting with shock is rare. PATIENT CONCERNS In this case, the condition of a 77-year-old immunocompromised patient with intermittent diarrhea progressed to shock and hypoalbuminemia. Reviewing her medical records, we learned that she had experienced intermittent peripheral eosinophilia during the past 10 months. Although a series of examinations were done, the disease progressed and the diagnosis remained uncertain. DIAGNOSIS Using standard microscopic stool examination and gastroduodenscopy with biopsy, a diagnosis of strongyloidiasis was made. INTERVENTIONS After the diagnosis of strongyloidiasis was made, 2 courses of ivermectin were administered. OUTCOMES The patient recovered uneventfully after treatment and there is no recurrence of eosinophilia in 1 year follow-up. LESSONS This report provides a brief review of the current modalities used for diagnosing strongyloidiasis. It emphasizes the low sensitivity of microscopic examination, and highlights the role of gastroduodenoscopy in the diagnosis of strongyloidiasis. This report also assures that patients with strongyloidiasis have a good prognosis when they are treated timely and appropriately.
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Affiliation(s)
- Jih Tze Tan
- School of Medicine, Tzu Chi University, Hualien, Taiwan (R.O.C.)
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan (R.O.C.)
| | - Chih-Wei Tseng
- School of Medicine, Tzu Chi University, Hualien, Taiwan (R.O.C.)
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan (R.O.C.)
- *Correspondence: Chih-Wei Tseng, Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin Township, Chiayi County 622, Taiwan (R.O.C.) (e-mail: )
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Zhang J, Li Y, Wan J, Zhang M, Li C, Lin J. Artesunate: A review of its therapeutic insights in respiratory diseases. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 104:154259. [PMID: 35849970 DOI: 10.1016/j.phymed.2022.154259] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 05/31/2022] [Accepted: 06/07/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Artesunate, as a semi-synthetic artemisinin derivative of sesquiterpene lactone, is widely used in clinical antimalarial treatment due to its endoperoxide group. Recent studies have found that artesunate may have multiple pharmacological effects, indicating its significant therapeutic potential in multiple respiratory diseases. PURPOSE This review aims to summarize proven and potential therapeutic effects of artesunate in common respiratory disorders. STUDY DESIGN This review summarizes the pharmacological properties of artesunate and then interprets the function of artesunate in various respiratory diseases in detail, such as bronchial asthma, chronic obstructive pulmonary disease, lung injury, lung cancer, pulmonary fibrosis, coronavirus disease 2019, etc., on different target cells and receptors according to completed and ongoing in silico, in vitro, and in vivo studies (including clinical trials). METHODS Literature was searched in electronic databases, including Pubmed, Web of Science and CNKI with the primary keywords of 'artesunate', 'pharmacology', 'pharmacokinetics', 'respiratory disorders', 'lung', 'pulmonary', and secondary search terms of 'Artemisia annua L.', 'artemisinin', 'asthma', 'chronic obstructive lung disease', 'lung injury', 'lung cancer', 'pulmonary fibrosis', 'COVID-19' and 'virus' in English and Chinese. All experiments were included. Reviews and irrelevant studies to the therapeutic effects of artesunate on respiratory diseases were excluded. Information was sort out according to study design, subject, intervention, and outcome. RESULTS Artesunate is promising to treat multiple common respiratory disorders via various mechanisms, such as anti-inflammation, anti-oxidative stress, anti-hyperresponsiveness, anti-proliferation, airway remodeling reverse, induction of cell death, cell cycle arrest, etc. CONCLUSION: Artesunate has great potential to treat various respiratory diseases.
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Affiliation(s)
- Jingyuan Zhang
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100-730, China; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100-029, China
| | - Yun Li
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100-029, China; Beijing University of Chinese Medicine, Beijing 100-029, China
| | - Jingxuan Wan
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100-730, China; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100-029, China
| | - Mengyuan Zhang
- Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100-730, China; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100-029, China
| | - Chunxiao Li
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100-029, China; Peking University China‑Japan Friendship School of Clinical Medicine, Beijing 100-029, China
| | - Jiangtao Lin
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100-029, China.
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Duan X, Lo SY, Lee JCY, Wan JMF, Yu ACH. Sonoporation of Immune Cells: Heterogeneous Impact on Lymphocytes, Monocytes and Granulocytes. ULTRASOUND IN MEDICINE & BIOLOGY 2022; 48:1268-1281. [PMID: 35461725 DOI: 10.1016/j.ultrasmedbio.2022.02.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 02/23/2022] [Accepted: 02/24/2022] [Indexed: 06/14/2023]
Abstract
Microbubble-mediated ultrasound (MB-US) can be used to realize sonoporation and, in turn, facilitate the transfection of leukocytes in the immune system. Nevertheless, the bio-effects that can be induced by MB-US exposure on leukocytes have not been adequately studied, particularly for different leukocyte lineage subsets with distinct cytological characteristics. Here, we describe how that same set of MB-US exposure conditions would induce heterogeneous bio-effects on the three main leukocyte subsets: lymphocytes, monocytes and granulocytes. MB-US exposure was delivered by applying 1-MHz pulsed ultrasound (0.50-MPa peak negative pressure, 10% duty cycle, 30-s exposure period) in the presence of microbubbles (1:1 cell-to-bubble ratio); sonoporated and non-viable leukocytes were respectively labeled using calcein and propidium iodide. Flow cytometry was then performed to classify leukocytes into their corresponding subsets and to analyze each subset's post-exposure viability, sonoporation rate, uptake characteristics and morphology. Results revealed that, when subjected to MB-US exposure, granulocytes experienced the highest loss of viability (64.0 ± 11.0%) and the lowest sonoporation rate (6.3 ± 2.5%), despite maintaining their size and granularity. In contrast, lymphocytes exhibited the lowest loss of viability (20.9 ± 7.0%), while monocytes had the highest sonoporation rate (24.1 ± 13.6%). For these two sonoporated leukocyte subsets, their cell size and granularity were found to be reduced. Also, they exhibited graded levels of calcein uptake, whereas sonoporated granulocytes achieved only mild calcein uptake. These heterogeneous bio-effects should be accounted for when using MB-US and sonoporation in immunomodulation applications.
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Affiliation(s)
- Xinxing Duan
- Schlegel Research Institute for Aging and Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, Ontario, Canada; School of Biological Sciences, University of Hong Kong, Pokfulam, Hong Kong, China
| | - Shun Yu Lo
- School of Biological Sciences, University of Hong Kong, Pokfulam, Hong Kong, China
| | - Jetty C Y Lee
- School of Biological Sciences, University of Hong Kong, Pokfulam, Hong Kong, China
| | - Jennifer M F Wan
- School of Biological Sciences, University of Hong Kong, Pokfulam, Hong Kong, China
| | - Alfred C H Yu
- Schlegel Research Institute for Aging and Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, Ontario, Canada.
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Mawhinney M, Kulle A, Thanabalasuriar A. From infection to repair: Understanding the workings of our innate immune cells. WIREs Mech Dis 2022; 14:e1567. [PMID: 35674186 DOI: 10.1002/wsbm.1567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 04/13/2022] [Accepted: 05/04/2022] [Indexed: 11/06/2022]
Abstract
In a world filled with microbes, some posing a threat to our body, our immune system is key to living a healthy life. The innate immune system is made of various cell types that act to guard our bodies. Unlike the adaptive immune system that has a specific response, our innate immune system encompasses cells that elicit unspecific immune responses, triggered whenever the right signals are detected. Our understanding of immunity started with the concept of our immune system only responding to "nonself" like the pathogens that invade our body. However, over the past few decades, we have learned that the immune system is more than an on/off switch that recognizes nonself. The innate immune system regularly patrols our bodies for pathogens and tissue damage. Our innate immune system not only seeks to resolve infection but also repair tissue injury, through phagocytosing debris and initiating the release of growth factors. Recently, we are starting to see that it is not just recognizing danger, our innate immune system plays a crucial role in repair. Innate immune cells phenotypically change during repair. In the context of severe injury or trauma, our innate immune system is modified quite drastically to help repair, resulting in reduced infection control. Moreover, these changes in immune cell function can be modified by sex as a biological variable. From past to present, in this overview, we provide a summary of the innate immune cells and pathways in infection and tissue repair. This article is categorized under: Immune System Diseases > Molecular and Cellular Physiology.
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Affiliation(s)
- Martin Mawhinney
- Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada
| | - Amelia Kulle
- Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada
| | - Ajitha Thanabalasuriar
- Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.,Department of Microbiology and Immunology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada
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Mengli Xu, Su J, Yue Z, Yu Y, Zhao X, Xie X. Inflammation and Limb Regeneration: The Role of the Chemokines. Russ J Dev Biol 2022. [DOI: 10.1134/s1062360422030055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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41
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Gürbüz M, Aktaç Ş. Understanding the role of vitamin A and its precursors in the immune system. NUTR CLIN METAB 2022. [DOI: 10.1016/j.nupar.2021.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Neutrophil Functional Heterogeneity and Implications for Viral Infections and Treatments. Cells 2022; 11:cells11081322. [PMID: 35456003 PMCID: PMC9025666 DOI: 10.3390/cells11081322] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 04/08/2022] [Accepted: 04/10/2022] [Indexed: 12/15/2022] Open
Abstract
Evidence suggests that neutrophils exert specialized effector functions during infection and inflammation, and that these cells can affect the duration, severity, and outcome of the infection. These functions are related to variations in phenotypes that have implications in immunoregulation during viral infections. Although the complexity of the heterogeneity of neutrophils is still in the process of being uncovered, evidence indicates that they display phenotypes and functions that can assist in viral clearance or augment and amplify the immunopathology of viruses. Therefore, deciphering and understanding neutrophil subsets and their polarization in viral infections is of importance. In this review, the different phenotypes of neutrophils and the roles they play in viral infections are discussed. We also examine the possible ways to target neutrophil subsets during viral infections as potential anti-viral treatments.
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Lin Z, Xia Y, Guo J, Xu G, Liu Y, Yang Y, Xie H, Huang Y, Fu Q. Caspase-1 deficiency impairs neutrophils recruitment and bacterial clearance in Streptococcus equi ssp. zooepidemicus infected mice. Vet Microbiol 2022; 268:109411. [DOI: 10.1016/j.vetmic.2022.109411] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 03/08/2022] [Accepted: 03/26/2022] [Indexed: 11/27/2022]
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Tumour cell apoptosis modulates the colorectal cancer immune microenvironment via interleukin-8-dependent neutrophil recruitment. Cell Death Dis 2022; 13:113. [PMID: 35121727 PMCID: PMC8816934 DOI: 10.1038/s41419-022-04585-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 01/10/2022] [Accepted: 01/26/2022] [Indexed: 12/21/2022]
Abstract
Sporadic apoptosis of tumour cells is a commonly observed feature of colorectal cancer (CRC) and strongly correlates with adverse patient prognosis. The uptake of apoptotic cell debris by neutrophils induces a non-inflammatory, pro-regenerative, and hence potentially pro-tumorigenic phenotype. In this study, we therefore sought to investigate the impact of apoptotic CRC cells on neutrophils and its consequence on other immune cells of the tumour microenvironment. Apoptosis induced by combined TNFα-treatment and UV-C irradiation, as well as various chemotherapeutic agents, led to a substantial release of neutrophil-attracting chemokines, most importantly interleukin-8 (IL-8), in both primary patient-derived and established CRC cells. Accordingly, conditioned media of apoptotic tumour cells selectively stimulated chemotaxis of neutrophils, but not T cells or monocytes. Notably, caspase-inhibition partially reduced IL-8 secretion, suggesting that caspase activity might be required for apoptosis-induced IL-8 release. Moreover, apoptotic tumour cell-conditioned media considerably prolonged neutrophil lifespan and induced an activated CD66bhighCD11bhighCD62Llow phenotype, comparable to that of tumour-associated neutrophils in CRC patients, as assessed by flow cytometry of dissociated CRC tissues. Immunohistochemical analyses of 35 CRC patients further revealed a preferential accumulation of neutrophils at sites of apoptotic tumour cells defined by the expression of epithelial cell-specific caspase-cleaved cytokeratin-18. The same areas were also highly infiltrated by macrophages, while T cells were virtually absent. Notably, neutrophils induced an M2-like CD86lowCD163+CD206+ phenotype in co-cultured monocyte-derived macrophages and suppressed LPS-induced pro-inflammatory cytokine release. In an in vitro transwell model, IL-8 blockade efficiently prevented neutrophil-induced anti-inflammatory macrophage polarisation by inhibiting neutrophil migration towards IL-8 gradients generated by apoptotic CRC cells. To conclude, our data suggest that apoptotic cancer cells release chemotactic factors that attract neutrophils into the tumour, where their interaction with neighbouring macrophages might promote an immunologically unfavourable tumour microenvironment. This effect may contribute to tumour recurrence after chemotherapy-induced apoptosis.
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Racca F, Pellegatta G, Cataldo G, Vespa E, Carlani E, Pelaia C, Paoletti G, Messina MR, Nappi E, Canonica GW, Repici A, Heffler E. Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets. Front Physiol 2022; 12:815842. [PMID: 35095572 PMCID: PMC8790151 DOI: 10.3389/fphys.2021.815842] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 12/09/2021] [Indexed: 12/11/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation, whose incidence is rising. It significantly affects patients’ quality of life and, if left untreated, results in fibrotic complications. Although broad consensus has been achieved on first-line therapy, a subset of patients remains non-responder to standard therapy. The pathogenesis of EoE is multifactorial and results from the complex, still mostly undefined, interaction between genetics and intrinsic factors, environment, and antigenic stimuli. A deep understanding of the pathophysiology of this disease is pivotal for the development of new therapies. This review provides a comprehensive description of the pathophysiology of EoE, starting from major pathogenic mechanisms (genetics, type 2 inflammation, epithelial barrier dysfunction, gastroesophageal reflux, allergens, infections and microbiota) and subsequently focusing on the single protagonists of type 2 inflammation (involved cells, cytokines, soluble effectors, surface proteins and transcription factors) that could represent present and future therapeutic targets, while summarizing previous therapeutic approaches in literature.
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Affiliation(s)
- Francesca Racca
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- *Correspondence: Francesca Racca,
| | - Gaia Pellegatta
- Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Giuseppe Cataldo
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Edoardo Vespa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Elisa Carlani
- Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Corrado Pelaia
- Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Giovanni Paoletti
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Maria Rita Messina
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Emanuele Nappi
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Giorgio Walter Canonica
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Enrico Heffler
- Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
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Meng J, Zhang G, Wang WX. Functional heterogeneity of immune defenses in molluscan oysters Crassostrea hongkongensis revealed by high-throughput single-cell transcriptome. FISH & SHELLFISH IMMUNOLOGY 2022; 120:202-213. [PMID: 34843943 DOI: 10.1016/j.fsi.2021.11.027] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 11/18/2021] [Accepted: 11/18/2021] [Indexed: 06/13/2023]
Abstract
Oyster is the worldwide aquaculture molluscan and evolves a complex immune defense system, with hemocytes as the major immune system for its host defense. However, the functional heterogeneity of hemocyte has not been characterized, which markedly hinders our understanding of its defense role. Here, we used the single-cell transcriptome profiling (scRNA-seq), which provides a high-resolution visual insight into its dynamics, to map the hemocyte and assess its heterogeneity in a molluscan oyster Crassostrea hongkongensis. By combining with the cell type specific RNA-seq, thirteen subpopulations belonging to granulocyte, semi-granulocyte, and hyalinocyte were revealed. The granulocytes mainly participated in immune response and autophagy process. Pseudo-temporal ordering of granulocytes identified two different cell-lineages. The hematopoietic transcription factors regulated networks controlling their differentiations were also identified. We further identified one subpopulation of granulocytes in immune activate states with the cell cycle and immune responsive genes expressions, which illustrated the functional heterogeneity of the same cell type. Collectively, our scRNA-seq analysis demonstrated the hemocytes diversity of molluscans. The results are important in our understanding of the immune defense evolution and functional differentiation of hemocytes in Phylum Mollusca.
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Affiliation(s)
- Jie Meng
- School of Energy and Environment and Hong Kong Branch of the Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon, Hong Kong, China; Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China
| | - Guofan Zhang
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
| | - Wen-Xiong Wang
- School of Energy and Environment and Hong Kong Branch of the Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon, Hong Kong, China; Research Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen, 518057, China.
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Tajbakhsh A, Gheibihayat SM, Mortazavi D, Medhati P, Rostami B, Savardashtaki A, Momtazi-Borojeni AA. The Effect of Cigarette Smoke Exposure on Efferocytosis in Chronic Obstructive Pulmonary Disease; Molecular Mechanisms and Treatment Opportunities. COPD 2021; 18:723-736. [PMID: 34865568 DOI: 10.1080/15412555.2021.1978419] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Cigarette smoking-related inflammation, cellular stresses, and tissue destruction play a key role in lung disease, such as chronic obstructive pulmonary disease (COPD). Notably, augmented apoptosis and impaired clearance of apoptotic cells, efferocytosis, contribute to the chronic inflammatory response and tissue destruction in patients with COPD. Of note, exposure to cigarette smoke can impair alveolar macrophages efferocytosis activity, which leads to secondary necrosis formation and tissue inflammation. A better understanding of the processes behind the effect of cigarette smoke on efferocytosis concerning lung disorders can help to design more efficient treatment approaches and also delay the development of lung disease, such as COPD. To this end, we aimed to seek mechanisms underlying the impairing effect of cigarette smoke on macrophages-mediated efferocytosis in COPD. Further, available therapeutic opportunities for restoring efferocytosis activity and ameliorating respiratory tract inflammation in smokers with COPD were also discussed.
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Affiliation(s)
- Amir Tajbakhsh
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Mohammad Gheibihayat
- Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Deniz Mortazavi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran
| | - Pourya Medhati
- Student research committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Behrouz Rostami
- Health & Treatment Center of Rostam, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Savardashtaki
- Epilepsy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Abbas Momtazi-Borojeni
- Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Iran's National Elites Foundation, Tehran, Iran
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48
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Capó X, Martorell M, Tur JA, Sureda A, Pons A. 5-Dodecanolide, a Compound Isolated from Pig Lard, Presents Powerful Anti-Inflammatory Properties. Molecules 2021; 26:7363. [PMID: 34885945 PMCID: PMC8658921 DOI: 10.3390/molecules26237363] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 11/26/2021] [Accepted: 11/27/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Pork lard (PL) is traditionally used as an anti-inflammatory agent. We propose to demonstrate the anti-inflammatory properties of PL, and elucidate which compounds could be responsible for the anti-inflammatory effects. METHODS The anti-inflammatory effects of PL were tested in a rat model of zymosan-induced hind paw inflammation. Further, the hydroalcoholic extract from PL was obtained, the composition analyzed, and the anti-inflammatory activity of the extracts and isolated components assayed using immune cells stimulated with lipopolysaccharide (LPS). RESULTS Applying the ointment on the inflamed rat feet reduced the foot diameter, foot weight, and activities of antioxidant enzymes and inflammatory markers of circulating neutrophils. The main components of the hydroalcoholic extract were 5-dodecanolide, oleamide, hexadecanoic acid, 9-octadecenoic acid, hexadecanamide, and resolvin D1. CONCLUSIONS PL reduces the immune response in an animal model stimulated with zymosan. Hydroalcoholic PL extract and its components (5-Dodecanolide, Oleamide, and Resolvin D1) exerted an anti-inflammatory effect on LPS-stimulated neutrophils and peripheral mononuclear cells reducing the capability to produce TNFα, as well as the activities of antioxidant and pro-inflammatory enzymes. These effects are attributable to 5-dodecanolide, although the effects of this compound alone do not reach the magnitude of the anti-inflammatory effects observed by the complete hydroalcoholic extract.
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Affiliation(s)
- Xavier Capó
- Research Group on Community Nutrition and Oxidative Stress, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain; (X.C.); (J.A.T.); (A.S.)
- Research Group on Community Nutrition and Oxidative Stress, Laboratory of Physical Activity Sciences, University of the Balearic Islands, 07122 Palma, Spain
| | - Miquel Martorell
- Department of Nutrition and Dietetics, Faculty of Pharmacy, Centre for Healthy Living, University of Concepcion, Concepcion 4070386, Chile;
| | - Josep A. Tur
- Research Group on Community Nutrition and Oxidative Stress, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain; (X.C.); (J.A.T.); (A.S.)
- Research Group on Community Nutrition and Oxidative Stress, Laboratory of Physical Activity Sciences, University of the Balearic Islands, 07122 Palma, Spain
- CIBEROBN (Physiopathology of Obesity and Nutrition CB12/03/30038), Carlos III Health Institute, 28029 Madrid, Spain
| | - Antoni Sureda
- Research Group on Community Nutrition and Oxidative Stress, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain; (X.C.); (J.A.T.); (A.S.)
- Research Group on Community Nutrition and Oxidative Stress, Laboratory of Physical Activity Sciences, University of the Balearic Islands, 07122 Palma, Spain
- CIBEROBN (Physiopathology of Obesity and Nutrition CB12/03/30038), Carlos III Health Institute, 28029 Madrid, Spain
| | - Antoni Pons
- Research Group on Community Nutrition and Oxidative Stress, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma, Spain; (X.C.); (J.A.T.); (A.S.)
- Research Group on Community Nutrition and Oxidative Stress, Laboratory of Physical Activity Sciences, University of the Balearic Islands, 07122 Palma, Spain
- CIBEROBN (Physiopathology of Obesity and Nutrition CB12/03/30038), Carlos III Health Institute, 28029 Madrid, Spain
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49
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Cossarizza A, Chang HD, Radbruch A, Abrignani S, Addo R, Akdis M, Andrä I, Andreata F, Annunziato F, Arranz E, Bacher P, Bari S, Barnaba V, Barros-Martins J, Baumjohann D, Beccaria CG, Bernardo D, Boardman DA, Borger J, Böttcher C, Brockmann L, Burns M, Busch DH, Cameron G, Cammarata I, Cassotta A, Chang Y, Chirdo FG, Christakou E, Čičin-Šain L, Cook L, Corbett AJ, Cornelis R, Cosmi L, Davey MS, De Biasi S, De Simone G, del Zotto G, Delacher M, Di Rosa F, Di Santo J, Diefenbach A, Dong J, Dörner T, Dress RJ, Dutertre CA, Eckle SBG, Eede P, Evrard M, Falk CS, Feuerer M, Fillatreau S, Fiz-Lopez A, Follo M, Foulds GA, Fröbel J, Gagliani N, Galletti G, Gangaev A, Garbi N, Garrote JA, Geginat J, Gherardin NA, Gibellini L, Ginhoux F, Godfrey DI, Gruarin P, Haftmann C, Hansmann L, Harpur CM, Hayday AC, Heine G, Hernández DC, Herrmann M, Hoelsken O, Huang Q, Huber S, Huber JE, Huehn J, Hundemer M, Hwang WYK, Iannacone M, Ivison SM, Jäck HM, Jani PK, Keller B, Kessler N, Ketelaars S, Knop L, Knopf J, Koay HF, Kobow K, Kriegsmann K, Kristyanto H, Krueger A, Kuehne JF, Kunze-Schumacher H, Kvistborg P, Kwok I, Latorre D, et alCossarizza A, Chang HD, Radbruch A, Abrignani S, Addo R, Akdis M, Andrä I, Andreata F, Annunziato F, Arranz E, Bacher P, Bari S, Barnaba V, Barros-Martins J, Baumjohann D, Beccaria CG, Bernardo D, Boardman DA, Borger J, Böttcher C, Brockmann L, Burns M, Busch DH, Cameron G, Cammarata I, Cassotta A, Chang Y, Chirdo FG, Christakou E, Čičin-Šain L, Cook L, Corbett AJ, Cornelis R, Cosmi L, Davey MS, De Biasi S, De Simone G, del Zotto G, Delacher M, Di Rosa F, Di Santo J, Diefenbach A, Dong J, Dörner T, Dress RJ, Dutertre CA, Eckle SBG, Eede P, Evrard M, Falk CS, Feuerer M, Fillatreau S, Fiz-Lopez A, Follo M, Foulds GA, Fröbel J, Gagliani N, Galletti G, Gangaev A, Garbi N, Garrote JA, Geginat J, Gherardin NA, Gibellini L, Ginhoux F, Godfrey DI, Gruarin P, Haftmann C, Hansmann L, Harpur CM, Hayday AC, Heine G, Hernández DC, Herrmann M, Hoelsken O, Huang Q, Huber S, Huber JE, Huehn J, Hundemer M, Hwang WYK, Iannacone M, Ivison SM, Jäck HM, Jani PK, Keller B, Kessler N, Ketelaars S, Knop L, Knopf J, Koay HF, Kobow K, Kriegsmann K, Kristyanto H, Krueger A, Kuehne JF, Kunze-Schumacher H, Kvistborg P, Kwok I, Latorre D, Lenz D, Levings MK, Lino AC, Liotta F, Long HM, Lugli E, MacDonald KN, Maggi L, Maini MK, Mair F, Manta C, Manz RA, Mashreghi MF, Mazzoni A, McCluskey J, Mei HE, Melchers F, Melzer S, Mielenz D, Monin L, Moretta L, Multhoff G, Muñoz LE, Muñoz-Ruiz M, Muscate F, Natalini A, Neumann K, Ng LG, Niedobitek A, Niemz J, Almeida LN, Notarbartolo S, Ostendorf L, Pallett LJ, Patel AA, Percin GI, Peruzzi G, Pinti M, Pockley AG, Pracht K, Prinz I, Pujol-Autonell I, Pulvirenti N, Quatrini L, Quinn KM, Radbruch H, Rhys H, Rodrigo MB, Romagnani C, Saggau C, Sakaguchi S, Sallusto F, Sanderink L, Sandrock I, Schauer C, Scheffold A, Scherer HU, Schiemann M, Schildberg FA, Schober K, Schoen J, Schuh W, Schüler T, Schulz AR, Schulz S, Schulze J, Simonetti S, Singh J, Sitnik KM, Stark R, Starossom S, Stehle C, Szelinski F, Tan L, Tarnok A, Tornack J, Tree TIM, van Beek JJP, van de Veen W, van Gisbergen K, Vasco C, Verheyden NA, von Borstel A, Ward-Hartstonge KA, Warnatz K, Waskow C, Wiedemann A, Wilharm A, Wing J, Wirz O, Wittner J, Yang JHM, Yang J. Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition). Eur J Immunol 2021; 51:2708-3145. [PMID: 34910301 PMCID: PMC11115438 DOI: 10.1002/eji.202170126] [Show More Authors] [Citation(s) in RCA: 274] [Impact Index Per Article: 68.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers.
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Affiliation(s)
- Andrea Cossarizza
- Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Hyun-Dong Chang
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
- Institute for Biotechnology, Technische Universität, Berlin, Germany
| | - Andreas Radbruch
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Sergio Abrignani
- Istituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi (INGM), Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Richard Addo
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Mübeccel Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Immanuel Andrä
- Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, Munich, Germany
| | - Francesco Andreata
- Division of Immunology, Transplantation and Infectious Diseases, IRCSS San Raffaele Scientific Institute, Milan, Italy
| | - Francesco Annunziato
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Eduardo Arranz
- Mucosal Immunology Lab, Unidad de Excelencia Instituto de Biomedicina y Genética Molecular de Valladolid (IBGM, Universidad de Valladolid-CSIC), Valladolid, Spain
| | - Petra Bacher
- Institute of Immunology, Christian-Albrechts Universität zu Kiel & Universitätsklinik Schleswig-Holstein, Kiel, Germany
- Institute of Clinical Molecular Biology Christian-Albrechts Universität zu Kiel, Kiel, Germany
| | - Sudipto Bari
- Division of Medical Sciences, National Cancer Centre Singapore, Singapore
- Cancer & Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore
| | - Vincenzo Barnaba
- Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy
- Center for Life Nano & Neuro Science@Sapienza, Istituto Italiano di Tecnologia (IIT), Rome, Italy
- Istituto Pasteur - Fondazione Cenci Bolognetti, Rome, Italy
| | | | - Dirk Baumjohann
- Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Bonn, Germany
| | - Cristian G. Beccaria
- Division of Immunology, Transplantation and Infectious Diseases, IRCSS San Raffaele Scientific Institute, Milan, Italy
| | - David Bernardo
- Mucosal Immunology Lab, Unidad de Excelencia Instituto de Biomedicina y Genética Molecular de Valladolid (IBGM, Universidad de Valladolid-CSIC), Valladolid, Spain
- Centro de Investigaciones Biomédicas en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain
| | - Dominic A. Boardman
- Department of Surgery, The University of British Columbia, Vancouver, Canada
- BC Children’s Hospital Research Institute, Vancouver, Canada
| | - Jessica Borger
- Department of Immunology and Pathology, Monash University, Melbourne, Victoria, Australia
| | - Chotima Böttcher
- Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Leonie Brockmann
- Department of Microbiology & Immunology, Columbia University, New York City, USA
| | - Marie Burns
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Dirk H. Busch
- Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, Munich, Germany
- German Center for Infection Research (DZIF), Munich, Germany
| | - Garth Cameron
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
- Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria, Australia
| | - Ilenia Cammarata
- Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy
| | - Antonino Cassotta
- Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland
| | - Yinshui Chang
- Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Bonn, Germany
| | - Fernando Gabriel Chirdo
- Instituto de Estudios Inmunológicos y Fisiopatológicos - IIFP (UNLP-CONICET), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina
| | - Eleni Christakou
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, UK
- National Institute for Health Research (NIHR) Biomedical Research Center (BRC), Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, London, UK
| | - Luka Čičin-Šain
- Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Laura Cook
- BC Children’s Hospital Research Institute, Vancouver, Canada
- Department of Medicine, The University of British Columbia, Vancouver, Canada
| | - Alexandra J. Corbett
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
| | - Rebecca Cornelis
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Lorenzo Cosmi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Martin S. Davey
- Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
| | - Sara De Biasi
- Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Gabriele De Simone
- Laboratory of Translational Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | | | - Michael Delacher
- Institute for Immunology, University Medical Center Mainz, Mainz, Germany
- Research Centre for Immunotherapy, University Medical Center Mainz, Mainz, Germany
| | - Francesca Di Rosa
- Institute of Molecular Biology and Pathology, National Research Council of Italy (CNR), Rome, Italy
- Immunosurveillance Laboratory, The Francis Crick Institute, London, UK
| | - James Di Santo
- Innate Immunity Unit, Department of Immunology, Institut Pasteur, Paris, France
- Inserm U1223, Paris, France
| | - Andreas Diefenbach
- Laboratory of Innate Immunity, Department of Microbiology, Infectious Diseases and Immunology, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
- Mucosal and Developmental Immunology, German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Jun Dong
- Cell Biology, German Rheumatism Research Center Berlin (DRFZ), An Institute of the Leibniz Association, Berlin, Germany
| | - Thomas Dörner
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
- Department of Medicine/Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Regine J. Dress
- Institute of Systems Immunology, Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Charles-Antoine Dutertre
- Institut National de la Sante Et de la Recherce Medicale (INSERM) U1015, Equipe Labellisee-Ligue Nationale contre le Cancer, Villejuif, France
| | - Sidonia B. G. Eckle
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
| | - Pascale Eede
- Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Maximilien Evrard
- Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore
| | - Christine S. Falk
- Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany
| | - Markus Feuerer
- Regensburg Center for Interventional Immunology (RCI), Regensburg, Germany
- Chair for Immunology, University Regensburg, Regensburg, Germany
| | - Simon Fillatreau
- Institut Necker Enfants Malades, INSERM U1151-CNRS, UMR8253, Paris, France
- Université de Paris, Paris Descartes, Faculté de Médecine, Paris, France
- AP-HP, Hôpital Necker Enfants Malades, Paris, France
| | - Aida Fiz-Lopez
- Mucosal Immunology Lab, Unidad de Excelencia Instituto de Biomedicina y Genética Molecular de Valladolid (IBGM, Universidad de Valladolid-CSIC), Valladolid, Spain
| | - Marie Follo
- Department of Medicine I, Lighthouse Core Facility, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Gemma A. Foulds
- John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK
- Centre for Health, Ageing and Understanding Disease (CHAUD), School of Science and Technology, Nottingham Trent University, Nottingham, UK
| | - Julia Fröbel
- Immunology of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute, Jena, Germany
| | - Nicola Gagliani
- Department of Medicine, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Germany
| | - Giovanni Galletti
- Laboratory of Translational Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Anastasia Gangaev
- Division of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Natalio Garbi
- Institute of Molecular Medicine and Experimental Immunology, Faculty of Medicine, University of Bonn, Germany
| | - José Antonio Garrote
- Mucosal Immunology Lab, Unidad de Excelencia Instituto de Biomedicina y Genética Molecular de Valladolid (IBGM, Universidad de Valladolid-CSIC), Valladolid, Spain
- Laboratory of Molecular Genetics, Servicio de Análisis Clínicos, Hospital Universitario Río Hortega, Gerencia Regional de Salud de Castilla y León (SACYL), Valladolid, Spain
| | - Jens Geginat
- Istituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi (INGM), Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Nicholas A. Gherardin
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
- Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria, Australia
| | - Lara Gibellini
- Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Florent Ginhoux
- Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore
- Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore
| | - Dale I. Godfrey
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
- Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria, Australia
| | - Paola Gruarin
- Istituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi (INGM), Milan, Italy
| | - Claudia Haftmann
- Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland
| | - Leo Hansmann
- Department of Hematology, Oncology, and Tumor Immunology, Charité - Universitätsmedizin Berlin (CVK), Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
- German Cancer Consortium (DKTK), partner site Berlin, Germany
| | - Christopher M. Harpur
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia
- Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia
| | - Adrian C. Hayday
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, UK
- National Institute for Health Research (NIHR) Biomedical Research Center (BRC), Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, London, UK
- Immunosurveillance Laboratory, The Francis Crick Institute, London, UK
| | - Guido Heine
- Division of Allergy, Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Daniela Carolina Hernández
- Innate Immunity, German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
- Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases, Rheumatology, Berlin, Germany
| | - Martin Herrmann
- Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Medicine 3 – Rheumatology and Immunology and Universitätsklinikum Erlangen, Erlangen, Germany
- Deutsches Zentrum für Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
| | - Oliver Hoelsken
- Laboratory of Innate Immunity, Department of Microbiology, Infectious Diseases and Immunology, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
- Mucosal and Developmental Immunology, German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Qing Huang
- Department of Surgery, The University of British Columbia, Vancouver, Canada
- BC Children’s Hospital Research Institute, Vancouver, Canada
| | - Samuel Huber
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Johanna E. Huber
- Institute for Immunology, Biomedical Center, Faculty of Medicine, LMU Munich, Planegg-Martinsried, Germany
| | - Jochen Huehn
- Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Michael Hundemer
- Department of Hematology, Oncology and Rheumatology, University Heidelberg, Heidelberg, Germany
| | - William Y. K. Hwang
- Cancer & Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore
- Department of Hematology, Singapore General Hospital, Singapore, Singapore
- Executive Offices, National Cancer Centre Singapore, Singapore
| | - Matteo Iannacone
- Division of Immunology, Transplantation and Infectious Diseases, IRCSS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
- Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Sabine M. Ivison
- Department of Surgery, The University of British Columbia, Vancouver, Canada
- BC Children’s Hospital Research Institute, Vancouver, Canada
| | - Hans-Martin Jäck
- Division of Molecular Immunology, Nikolaus-Fiebiger-Center, Department of Internal Medicine III, University of Erlangen-Nürnberg, Erlangen, Germany
| | - Peter K. Jani
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Baerbel Keller
- Department of Rheumatology and Clinical Immunology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Center for Chronic Immunodeficiency, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Nina Kessler
- Institute of Molecular Medicine and Experimental Immunology, Faculty of Medicine, University of Bonn, Germany
| | - Steven Ketelaars
- Division of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Laura Knop
- Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Magdeburg, Germany
| | - Jasmin Knopf
- Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Medicine 3 – Rheumatology and Immunology and Universitätsklinikum Erlangen, Erlangen, Germany
- Deutsches Zentrum für Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
| | - Hui-Fern Koay
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
- Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria, Australia
| | - Katja Kobow
- Department of Neuropathology, Universitätsklinikum Erlangen, Germany
| | - Katharina Kriegsmann
- Department of Hematology, Oncology and Rheumatology, University Heidelberg, Heidelberg, Germany
| | - H. Kristyanto
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Andreas Krueger
- Institute for Molecular Medicine, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - Jenny F. Kuehne
- Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany
| | - Heike Kunze-Schumacher
- Institute for Molecular Medicine, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - Pia Kvistborg
- Division of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Immanuel Kwok
- Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore
| | | | - Daniel Lenz
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Megan K. Levings
- Department of Surgery, The University of British Columbia, Vancouver, Canada
- BC Children’s Hospital Research Institute, Vancouver, Canada
- School of Biomedical Engineering, The University of British Columbia, Vancouver, Canada
| | - Andreia C. Lino
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Francesco Liotta
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Heather M. Long
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Enrico Lugli
- Laboratory of Translational Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Katherine N. MacDonald
- BC Children’s Hospital Research Institute, Vancouver, Canada
- School of Biomedical Engineering, The University of British Columbia, Vancouver, Canada
- Michael Smith Laboratories, The University of British Columbia, Vancouver, Canada
| | - Laura Maggi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Mala K. Maini
- Division of Infection & Immunity, Institute of Immunity & Transplantation, University College London, London, UK
| | - Florian Mair
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Calin Manta
- Department of Hematology, Oncology and Rheumatology, University Heidelberg, Heidelberg, Germany
| | - Rudolf Armin Manz
- Institute for Systemic Inflammation Research, University of Luebeck, Luebeck, Germany
| | | | - Alessio Mazzoni
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - James McCluskey
- Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
| | - Henrik E. Mei
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Fritz Melchers
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Susanne Melzer
- Clinical Trial Center Leipzig, Leipzig University, Härtelstr.16, −18, Leipzig, 04107, Germany
| | - Dirk Mielenz
- Division of Molecular Immunology, Nikolaus-Fiebiger-Center, Department of Internal Medicine III, University of Erlangen-Nürnberg, Erlangen, Germany
| | - Leticia Monin
- Immunosurveillance Laboratory, The Francis Crick Institute, London, UK
| | - Lorenzo Moretta
- Department of Immunology, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
| | - Gabriele Multhoff
- Radiation Immuno-Oncology Group, Center for Translational Cancer Research (TranslaTUM), Technical University of Munich (TUM), Klinikum rechts der Isar, Munich, Germany
- Department of Radiation Oncology, Technical University of Munich (TUM), Klinikum rechts der Isar, Munich, Germany
| | - Luis Enrique Muñoz
- Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Medicine 3 – Rheumatology and Immunology and Universitätsklinikum Erlangen, Erlangen, Germany
- Deutsches Zentrum für Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
| | - Miguel Muñoz-Ruiz
- Immunosurveillance Laboratory, The Francis Crick Institute, London, UK
| | - Franziska Muscate
- Department of Medicine, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ambra Natalini
- Institute of Molecular Biology and Pathology, National Research Council of Italy (CNR), Rome, Italy
| | - Katrin Neumann
- Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lai Guan Ng
- Division of Medical Sciences, National Cancer Centre Singapore, Singapore
- Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore
- Department of Microbiology & Immunology, Immunology Programme, Life Science Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
| | | | - Jana Niemz
- Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | | | - Samuele Notarbartolo
- Istituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi (INGM), Milan, Italy
| | - Lennard Ostendorf
- Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Laura J. Pallett
- Division of Infection & Immunity, Institute of Immunity & Transplantation, University College London, London, UK
| | - Amit A. Patel
- Institut National de la Sante Et de la Recherce Medicale (INSERM) U1015, Equipe Labellisee-Ligue Nationale contre le Cancer, Villejuif, France
| | - Gulce Itir Percin
- Immunology of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute, Jena, Germany
| | - Giovanna Peruzzi
- Center for Life Nano & Neuro Science@Sapienza, Istituto Italiano di Tecnologia (IIT), Rome, Italy
| | - Marcello Pinti
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - A. Graham Pockley
- John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK
- Centre for Health, Ageing and Understanding Disease (CHAUD), School of Science and Technology, Nottingham Trent University, Nottingham, UK
| | - Katharina Pracht
- Division of Molecular Immunology, Nikolaus-Fiebiger-Center, Department of Internal Medicine III, University of Erlangen-Nürnberg, Erlangen, Germany
| | - Immo Prinz
- Institute of Immunology, Hannover Medical School, Hannover, Germany
- Institute of Systems Immunology, Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Irma Pujol-Autonell
- National Institute for Health Research (NIHR) Biomedical Research Center (BRC), Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, London, UK
- Peter Gorer Department of Immunobiology, King’s College London, London, UK
| | - Nadia Pulvirenti
- Istituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi (INGM), Milan, Italy
| | - Linda Quatrini
- Department of Immunology, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy
| | - Kylie M. Quinn
- School of Biomedical and Health Sciences, RMIT University, Bundorra, Victoria, Australia
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
| | - Helena Radbruch
- Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Hefin Rhys
- Flow Cytometry Science Technology Platform, The Francis Crick Institute, London, UK
| | - Maria B. Rodrigo
- Institute of Molecular Medicine and Experimental Immunology, Faculty of Medicine, University of Bonn, Germany
| | - Chiara Romagnani
- Innate Immunity, German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
- Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases, Rheumatology, Berlin, Germany
| | - Carina Saggau
- Institute of Immunology, Christian-Albrechts Universität zu Kiel & Universitätsklinik Schleswig-Holstein, Kiel, Germany
| | | | - Federica Sallusto
- Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland
- Institute of Microbiology, ETH Zurich, Zurich, Switzerland
| | - Lieke Sanderink
- Regensburg Center for Interventional Immunology (RCI), Regensburg, Germany
- Chair for Immunology, University Regensburg, Regensburg, Germany
| | - Inga Sandrock
- Institute of Immunology, Hannover Medical School, Hannover, Germany
| | - Christine Schauer
- Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Medicine 3 – Rheumatology and Immunology and Universitätsklinikum Erlangen, Erlangen, Germany
- Deutsches Zentrum für Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
| | - Alexander Scheffold
- Institute of Immunology, Christian-Albrechts Universität zu Kiel & Universitätsklinik Schleswig-Holstein, Kiel, Germany
| | - Hans U. Scherer
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Matthias Schiemann
- Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, Munich, Germany
| | - Frank A. Schildberg
- Clinic for Orthopedics and Trauma Surgery, University Hospital Bonn, Bonn, Germany
| | - Kilian Schober
- Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, Munich, Germany
- Mikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Germany
| | - Janina Schoen
- Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Medicine 3 – Rheumatology and Immunology and Universitätsklinikum Erlangen, Erlangen, Germany
- Deutsches Zentrum für Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
| | - Wolfgang Schuh
- Division of Molecular Immunology, Nikolaus-Fiebiger-Center, Department of Internal Medicine III, University of Erlangen-Nürnberg, Erlangen, Germany
| | - Thomas Schüler
- Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Magdeburg, Germany
| | - Axel R. Schulz
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Sebastian Schulz
- Division of Molecular Immunology, Nikolaus-Fiebiger-Center, Department of Internal Medicine III, University of Erlangen-Nürnberg, Erlangen, Germany
| | - Julia Schulze
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Sonia Simonetti
- Institute of Molecular Biology and Pathology, National Research Council of Italy (CNR), Rome, Italy
| | - Jeeshan Singh
- Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Department of Medicine 3 – Rheumatology and Immunology and Universitätsklinikum Erlangen, Erlangen, Germany
- Deutsches Zentrum für Immuntherapie, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
| | - Katarzyna M. Sitnik
- Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Regina Stark
- Charité Universitätsmedizin Berlin – BIH Center for Regenerative Therapies, Berlin, Germany
- Sanquin Research – Adaptive Immunity, Amsterdam, The Netherlands
| | - Sarah Starossom
- Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
| | - Christina Stehle
- Innate Immunity, German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
- Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases, Rheumatology, Berlin, Germany
| | - Franziska Szelinski
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
- Department of Medicine/Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Leonard Tan
- Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore
- Department of Microbiology & Immunology, Immunology Programme, Life Science Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Attila Tarnok
- Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany
- Department of Precision Instrument, Tsinghua University, Beijing, China
- Department of Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany
| | - Julia Tornack
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
| | - Timothy I. M. Tree
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, UK
- National Institute for Health Research (NIHR) Biomedical Research Center (BRC), Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, London, UK
| | - Jasper J. P. van Beek
- Laboratory of Translational Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Willem van de Veen
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | | | - Chiara Vasco
- Istituto Nazionale di Genetica Molecolare Romeo ed Enrica Invernizzi (INGM), Milan, Italy
| | - Nikita A. Verheyden
- Institute for Molecular Medicine, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - Anouk von Borstel
- Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
| | - Kirsten A. Ward-Hartstonge
- Department of Surgery, The University of British Columbia, Vancouver, Canada
- BC Children’s Hospital Research Institute, Vancouver, Canada
| | - Klaus Warnatz
- Department of Rheumatology and Clinical Immunology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Center for Chronic Immunodeficiency, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Claudia Waskow
- Immunology of Aging, Leibniz Institute on Aging – Fritz Lipmann Institute, Jena, Germany
- Institute of Biochemistry and Biophysics, Faculty of Biological Sciences, Friedrich-Schiller-University Jena, Jena, Germany
- Department of Medicine III, Technical University Dresden, Dresden, Germany
| | - Annika Wiedemann
- German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
- Department of Medicine/Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Anneke Wilharm
- Institute of Immunology, Hannover Medical School, Hannover, Germany
| | - James Wing
- Immunology Frontier Research Center, Osaka University, Japan
| | - Oliver Wirz
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
| | - Jens Wittner
- Division of Molecular Immunology, Nikolaus-Fiebiger-Center, Department of Internal Medicine III, University of Erlangen-Nürnberg, Erlangen, Germany
| | - Jennie H. M. Yang
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, UK
- National Institute for Health Research (NIHR) Biomedical Research Center (BRC), Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, London, UK
| | - Juhao Yang
- Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
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Tang L, He S, Yin Y, Liu H, Hu J, Cheng J, Wang W. Combination of Nanomaterials in Cell-Based Drug Delivery Systems for Cancer Treatment. Pharmaceutics 2021; 13:pharmaceutics13111888. [PMID: 34834304 PMCID: PMC8621332 DOI: 10.3390/pharmaceutics13111888] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 10/22/2021] [Accepted: 11/03/2021] [Indexed: 02/07/2023] Open
Abstract
Cell-based drug delivery systems have shown tremendous advantages in cancer treatment due to their distinctive properties. For instance, delivery of therapeutics using tumor-tropic cells like neutrophils, lymphocytes and mesenchymal stem cells can achieve specific tumor targeting due to the "Trojan Horse" effect. Other circulatory cells like erythrocytes and platelets can greatly improve the circulation time of nanoparticles due to their innate long circulation property. Adipocytes, especially cancer-associated adipocytes, play key roles in tumor development and metabolism, therefore, adipocytes are regarded as promising bio-derived nanoplatforms for anticancer targeted drug delivery. Nanomaterials are important participants in cell-based drug delivery because of their unique physicochemical characteristics. Therefore, the integration of various nanomaterials with different cell types will endow the constructed delivery systems with many attractive properties due to the merits of both. In this review, a number of strategies based on nanomaterial-involved cell-mediated drug delivery systems for cancer treatment will be summarized. This review discusses how nanomaterials can be a benefit to cell-based therapies and how cell-derived carriers overcome the limitations of nanomaterials, which highlights recent advancements and specific biomedical applications based on nanomaterial-mediated, cell-based drug delivery systems.
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Affiliation(s)
- Lu Tang
- State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China; (L.T.); (S.H.); (Y.Y.); (H.L.); (J.H.)
- NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 211198, China
| | - Shun He
- State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China; (L.T.); (S.H.); (Y.Y.); (H.L.); (J.H.)
- NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 211198, China
| | - Yue Yin
- State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China; (L.T.); (S.H.); (Y.Y.); (H.L.); (J.H.)
- NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 211198, China
| | - Hening Liu
- State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China; (L.T.); (S.H.); (Y.Y.); (H.L.); (J.H.)
- NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 211198, China
| | - Jingyi Hu
- State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China; (L.T.); (S.H.); (Y.Y.); (H.L.); (J.H.)
- NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 211198, China
| | - Jie Cheng
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210029, China
- Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 211166, China
- Correspondence: (J.C.); (W.W.)
| | - Wei Wang
- State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China; (L.T.); (S.H.); (Y.Y.); (H.L.); (J.H.)
- NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 211198, China
- Correspondence: (J.C.); (W.W.)
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