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Kaur H, Thakur K, Parsad D, Kumar R. Therapeutic implications of baricitinib in mouse model of vitiligo. Arch Dermatol Res 2025; 317:353. [PMID: 39918618 DOI: 10.1007/s00403-025-03879-8] [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: 12/10/2024] [Revised: 01/15/2025] [Accepted: 01/18/2025] [Indexed: 02/09/2025]
Abstract
INTRODUCTION Vitiligo, an autoimmune disorder marked by skin depigmentation, is closely linked to immune dysregulation, including T cell infiltration and pro-inflammatory cytokines. This study explores the potential of baricitinib, a JAK-STAT inhibitor, in promoting repigmentation in vitiligo lesions by modulating immune responses. METHODS Using a mouse model of vitiligo induced by hydroquinone, we assessed the effects of baricitinib treatment on lesion repigmentation, CD8 + T cell infiltration, T cell populations, and serum TNF-α levels. Immunostaining, flow cytometry, and ELISA were used to analyse these parameters. RESULTS Baricitinib treatment significantly reduced CD8 + T cell infiltration in the skin, lowered serum TNF-α levels, and decreased both CD4 + and CD8 + T cell populations in the blood. Remarkably, these immune modulations correlated with notable repigmentation of the lesions. CONCLUSION Baricitinib effectively reduces inflammation and T cell infiltration, suggesting it as a promising therapeutic for vitiligo. These findings highlight its potential to modulate immune responses and restore skin pigmentation in vitiligo patients.
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Affiliation(s)
- Harjot Kaur
- Department of Zoology, Panjab University, Chandigarh, 160014, India
| | - Kanika Thakur
- Department of Zoology, Panjab University, Chandigarh, 160014, India
| | - Davinder Parsad
- Department of Dermatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Ravinder Kumar
- Department of Zoology, Panjab University, Chandigarh, 160014, India.
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Briganti S, Mosca S, Di Nardo A, Flori E, Ottaviani M. New Insights into the Role of PPARγ in Skin Physiopathology. Biomolecules 2024; 14:728. [PMID: 38927131 PMCID: PMC11201613 DOI: 10.3390/biom14060728] [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: 05/14/2024] [Revised: 06/17/2024] [Accepted: 06/18/2024] [Indexed: 06/28/2024] Open
Abstract
Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor expressed in many tissues, including skin, where it is essential for maintaining skin barrier permeability, regulating cell proliferation/differentiation, and modulating antioxidant and inflammatory responses upon ligand binding. Therefore, PPARγ activation has important implications for skin homeostasis. Over the past 20 years, with increasing interest in the role of PPARs in skin physiopathology, considerable effort has been devoted to the development of PPARγ ligands as a therapeutic option for skin inflammatory disorders. In addition, PPARγ also regulates sebocyte differentiation and lipid production, making it a potential target for inflammatory sebaceous disorders such as acne. A large number of studies suggest that PPARγ also acts as a skin tumor suppressor in both melanoma and non-melanoma skin cancers, but its role in tumorigenesis remains controversial. In this review, we have summarized the current state of research into the role of PPARγ in skin health and disease and how this may provide a starting point for the development of more potent and selective PPARγ ligands with a low toxicity profile, thereby reducing unwanted side effects.
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Affiliation(s)
| | | | | | - Enrica Flori
- Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, Italy; (S.B.); (S.M.); (A.D.N.); (M.O.)
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3
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Liu C, Liu X, Xin H, Li X. A Mendelian randomization study on the causal effects of circulating cytokines on the risk of vitiligo. Front Med (Lausanne) 2024; 11:1375339. [PMID: 38695020 PMCID: PMC11061512 DOI: 10.3389/fmed.2024.1375339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 03/12/2024] [Indexed: 05/04/2024] Open
Abstract
Background Accumulating evidence reveals an association between circulating cytokine levels and vitiligo. However, the causal association between circulating cytokine levels and vitiligo remains unrevealed. Methods We performed a two-sample Mendelian randomization (MR) analysis using a genome-wide association study of the 41 cytokines dataset, which was conducted with 3 Finnish cohorts (n = 8,293). Vitiligo data were acquired from strictly defined vitiligo data collected by FinnGenbiobank analysis, which included 207,613 European ancestors (131 vitiligo patients, 207,482 controls). The inverse-variance weighted (IVW) method, weighted median (WME), simple model, weighted model, and MR-Egger were used to determine the changes in vitiligo pathogenic cytokine taxa, followed by sensitivity analysis, including horizontal pleiotropy analysis. The MR Steiger test evaluated the strength of a causal association, and the leave-one-out method was used to assess the reliability of the results. The possibility of reverse causality was also investigated using a reverse MR study. Results We observed that rising IL-4 levels generated an enhanced probability of vitiligo in IVW (OR 2.72, 95%CI 1.19-6.22, p = 0.018). According to the results of the MR analysis, there were causal links between IL-4 and vitiligo. Results were steady after sensitivity and heterogeneity analyses. Conclusion Our research reveals that a genetically determined increased level of circulating IL-4 may be linked to a higher risk of developing vitiligo. The development of innovative treatment approaches (such as tofacitinib or dupilumab) that focus on blocking IL-4 as a novel way of preventing and treating vitiligo is significantly impacted by our findings.
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Affiliation(s)
- Chengling Liu
- Center of Burns and Plastic Surgery and Dermatology, The 924th Hospital of Joint Logistics Support Force of the PLA, Guilin, China
| | - Xingchen Liu
- Department of Pathology, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Haiming Xin
- Center of Burns and Plastic Surgery and Dermatology, The 924th Hospital of Joint Logistics Support Force of the PLA, Guilin, China
| | - Xin Li
- Center of Burns and Plastic Surgery and Dermatology, The 924th Hospital of Joint Logistics Support Force of the PLA, Guilin, China
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Zhao S, Chen X, Dutta K, Chen J, Wang J, Zhang Q, Jia H, Sun J, Lai Y. Multiple gene-drug prediction tool reveals Rosiglitazone based treatment pathway for non-segmental vitiligo. Inflammation 2024; 47:678-695. [PMID: 38159176 DOI: 10.1007/s10753-023-01937-9] [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: 06/26/2023] [Revised: 10/15/2023] [Accepted: 11/21/2023] [Indexed: 01/03/2024]
Abstract
Vitiligo is a skin disease characterized by selective loss of melanocytes, which seriously affects the appearance and causes great psychological stress to patients. In this study, we performed a comprehensive analysis of two vitiligo microarray datasets from the GEO database using bioinformatics tools to identify 297 up-regulated mRNAs and 186 down-regulated mRNAs, revealing important roles for pathways related to melanin synthesis, tyrosine metabolism, and inflammatory factors, such as "PPAR signaling pathway", "tyrosine metabolism", "nonalcoholic fatty liver disease (NAFLD) pathway", "melanogenesis", and "IL-17 signaling pathway". Combining the Search Tool for Interacting Chemicals (STITCH) database 5.0 and the drug-gene interaction database 3.0 (DGIdb), we identified that the PPAR-γ agonist rosiglitazone may promote melanin synthesis via EDNRB. Next, we investigated the mechanism of rosiglitazone and PPAR-γ pathway in promoting melanin production. Consistent with the results of bioinformatics analysis, the expression levels of PPAR-γ, EDNRB, and TYR were significantly reduced in human non-segmental vitiligo skin along with the reduction of MITF, a key gene for epidermal melanogenesis. Meanwhile, rosiglitazone increased melanin synthesis capacity in melanocytes and zebrafish by activating PPAR-γ and upregulating TYR, TYRP-1, and TYRP-2. Conversely, treatment of melanocytes with the PPAR-γ antagonist GW resulted in inhibition of melanin synthesis and expression of melanin-related factors. At the same time, simultaneous treatment of rosiglitazone with GW reversed the inhibitory effect of GW on melanin synthesis. In this study, we identified that rosiglitazone, an important insulin sensitizer, promotes melanin synthesis in melanocytes by increasing PPAR-γ activity and upregulating the expression levels of EDNRB and TYR. These findings may provide new ideas for exploring the pathogenesis and potential therapeutic targets of non-segmental vitiligo.
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Affiliation(s)
- Sijia Zhao
- Department of dermatologic Surgery, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xi Chen
- Department of Dermatology, Allergology and Venereology, Universitätsklinikum Schleswig-Holstein, Lübeck, Schleswig-Holstein, Germany
| | - Kuheli Dutta
- Department of Dermatology, Allergology and Venereology, Universitätsklinikum Schleswig-Holstein, Lübeck, Schleswig-Holstein, Germany
| | - Jia Chen
- Department of dermatologic Surgery, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Juan Wang
- School of Medicine, Shanghai University, Shanghai, China
| | - Qian Zhang
- Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People's Republic of China
| | - Hong Jia
- Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People's Republic of China
| | - Jianfang Sun
- Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People's Republic of China.
| | - Yongxian Lai
- Department of dermatologic Surgery, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
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5
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Keum H, Bermas B, Patel S, Jacobe HT, Chong BF. Patients with autoimmune skin diseases are at increased risk of adverse pregnancy outcomes. Am J Obstet Gynecol MFM 2024; 6:101226. [PMID: 37972926 DOI: 10.1016/j.ajogmf.2023.101226] [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: 08/22/2023] [Revised: 11/06/2023] [Accepted: 11/10/2023] [Indexed: 11/19/2023]
Abstract
BACKGROUND Increased rates of adverse pregnancy outcomes have been reported in association with rheumatologic diseases such as systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis. However, little is known about pregnancy outcomes in patients with autoimmune skin diseases. OBJECTIVE This study aimed to determine the frequency of adverse pregnancy outcomes in patients with autoimmune skin diseases. We hypothesized that similar to rheumatic diseases, the rate of adverse pregnancy outcomes in patients with autoimmune skin diseases would be higher than the general population. STUDY DESIGN This is a case control study using the TriNetX US Collaborative Network, which is a database of electronic medical records of >95 million patients seen at 57 healthcare organizations in the United States. All pregnant women between the ages of 15 and 44 years who were seen at a healthcare organization between January 1, 2016 and December 31, 2021 were included. Participants with autoimmune skin disease were matched to healthy controls and controls with systemic rheumatologic conditions (systemic lupus erythematosus or rheumatoid arthritis). For both the autoimmune skin disease and healthy control groups, those with systemic rheumatologic condition or hidradenitis suppurativa were excluded. The primary outcomes were adverse pregnancy outcomes defined as spontaneous abortion, gestational hypertension, preeclampsia or eclampsia, gestational diabetes mellitus, intrauterine growth restriction, preterm premature rupture of membranes, preterm birth, and stillbirth. Patients with autoimmune skin diseases and controls were 1:1 propensity score-matched by age, race, ethnicity, comorbidities, obesity, and substance use. For each outcome, odds ratio with a 95% confidence interval was calculated. RESULTS A total of 2788 patients with autoimmune skin diseases were matched to 2788 healthy controls. Patients with autoimmune skin diseases were at a higher risk of spontaneous abortions than controls (odds ratio, 1.54; 95% confidence interval, 1.36-1.75; P<.001). Compared with patients with systemic lupus erythematosus, patients with autoimmune skin diseases were at lower risk of having infants with intrauterine growth restriction (odds ratio, 0.59; 95% confidence interval, 0.4-0.87; P=.01), preterm birth (odds ratio, 0.68; 95% confidence interval, 0.47-0.98; P=.04), and stillbirth (odds ratio, 0.50; 95% confidence interval, 0.25-0.97; P=.04). The differences in adverse pregnancy outcomes between patients with autoimmune skin diseases and those with rheumatoid arthritis were not statistically significant. CONCLUSION Patients with autoimmune skin diseases are at a higher risk of spontaneous abortions than patients without autoimmune skin diseases. When analyzed by each autoimmune skin disease, patients with cutaneous lupus erythematosus or vitiligo remained at increased risk of spontaneous abortions compared with patients without autoimmune skin diseases. Patients with autoimmune skin diseases have similar risks of adverse pregnancy outcomes as patients with rheumatoid arthritis, but lower risks than patients with systemic lupus erythematosus.
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Affiliation(s)
- Heejo Keum
- Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, TX (Ms Keum, Drs Jacobe and Chong)
| | - Bonnie Bermas
- Division of Rheumatology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX (Dr Bermas)
| | - Shivani Patel
- Department of Obstetrics and Gynecology, The University of Texas Southwestern Medical Center, Dallas, TX (Dr Patel)
| | - Heidi T Jacobe
- Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, TX (Ms Keum, Drs Jacobe and Chong)
| | - Benjamin F Chong
- Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, TX (Ms Keum, Drs Jacobe and Chong).
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Han S, Cai L, Chen P, Kuang W. A study of the correlation between stroke and gut microbiota over the last 20years: a bibliometric analysis. Front Microbiol 2023; 14:1191758. [PMID: 37350780 PMCID: PMC10282156 DOI: 10.3389/fmicb.2023.1191758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 05/19/2023] [Indexed: 06/24/2023] Open
Abstract
Purpose This study intends to uncover a more thorough knowledge structure, research hotspots, and future trends in the field by presenting an overview of the relationship between stroke and gut microbiota in the past two decades. Method Studies on stroke and gut microbiota correlations published between 1st January 2002 and 31st December 2021 were retrieved from the Web of Science Core Collection and then visualized and scientometrically analyzed using CiteSpace V. Results A total of 660 papers were included in the study, among which the United States, the United Kingdom, and Germany were the leading research centers. Cleveland Clinic, Southern Medical University, and Chinese Academy of Science were the top three institutions. The NATURE was the most frequently co-cited journal. STANLEY L HAZEN was the most published author, and Tang WHW was the most cited one. The co-occurrence analysis revealed eight clusters (i.e., brain-gut microbiota axis, fecal microbiome transplantation, gut microbiota, hypertension, TMAO, ischemic stroke, neuroinflammation, atopobiosis). "gut microbiota," "Escherichia coli," "cardiovascular disease," "risk," "disease," "ischemic stroke," "stroke," "metabolism," "inflammation," and "phosphatidylcholine" were the most recent keyword explosions. Conclusion Findings suggest that in the next 10 years, the number of publications produced annually may increase significantly. Future research trends tend to concentrate on the mechanisms of stroke and gut microbiota, with the inflammation and immunological mechanisms, TMAO, and fecal transplantation as hotspots. And the relationship between these mechanisms and a particular cardiovascular illness may also be a future research trend.
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Affiliation(s)
- Shengnan Han
- Clinical Medical College of Acupuncture, Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Longhui Cai
- First School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Peipei Chen
- School of Medical Technology, Qiqihar Medical College, Qiqihar, Heilongjiang, China
| | - Weihong Kuang
- Guangdong Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China
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7
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Tsai TF, Ng CY. COVID-19 vaccine-associated vitiligo: A cross-sectional study in a tertiary referral center and systematic review. J Dermatol 2023. [PMID: 37186102 DOI: 10.1111/1346-8138.16799] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 03/02/2023] [Accepted: 03/21/2023] [Indexed: 05/17/2023]
Abstract
As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus continues to infect patients globally, vaccination remains one of the primary methods to combat this prolonged pandemic. However, there are growing reports of coronavirus disease 2019 (COVID-19) vaccines possibly triggering autoimmunity, irrespective of the vaccine's design. This phenomenon has been observed in patients with vitiligo, with a rising number of cases reporting new-onset or worsening vitiligo following COVID-19 vaccinations. In this study, the authors present the most extensive case series of COVID-19 vaccine-associated vitiligo to date, along with a systematic review of the literature. The aim is to assist physicians in the clinical evaluation of patients with vitiligo with regard to future vaccinations.
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Affiliation(s)
- Tsung-Fu Tsai
- Department of Dermatology, Chang Gung Memorial Hospital, Taipei, Taiwan
- Vitiligo Clinic and Pigment Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chau Yee Ng
- Department of Dermatology, Chang Gung Memorial Hospital, Taipei, Taiwan
- Vitiligo Clinic and Pigment Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Dermatology and Aesthetic Medicine Center, Jen Ai Hospital, Taichung, Taiwan
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8
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Beyzaee AM, Goldust M, Patil A, Rokni GR, Beyzaee S. The role of cytokines and vitamin D in vitiligo pathogenesis. J Cosmet Dermatol 2022; 21:6314-6325. [PMID: 35871394 DOI: 10.1111/jocd.15272] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 07/06/2022] [Accepted: 07/08/2022] [Indexed: 12/27/2022]
Abstract
Vitiligo is a pigment-related disease with a global prevalence of 0.2% to 1.8% associated with considerable burden on quality of life. The treatment is still a challenge because of relapses and/or incomplete re-pigmentation. Although the exact cause is still unclear, its pathogenesis seems to be justifiable with the autoimmune theory, supported by the results of clinical research. In this narrative review, we aimed to summarize the evidence related to cytokines and vitiligo development. This review is consisted of English articles published in PubMed and Google Scholar concerning levels of inflammatory mediators, especially interleukins, in vitiligo patients over the last 20 years. References of relevant articles were also considered for review. Crucial role of dysregulated levels of interleukins and their synergistic function to each other, in the onset or progression of the disease is evident. The theory of autoimmune vitiligo is reinforced by the results of the studies in the literature, due to the association of pathogenesis with increased secretion of pro-inflammatory mediators and reduction of anti-inflammatory mediators. Decreased vitamin D levels may have a considerable role in vitiligo development by affecting Th1- and Th17-related immune responses. Cytokines play an important role in the pathogenesis or progression of the disease. Moreover, we believe that decreased vitamin D level has a considerable role in vitiligo development by affecting Th1- and Th17-related immune responses.
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Affiliation(s)
| | - Mohamad Goldust
- Department of Dermatology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Anant Patil
- Department of Pharmacology, Dr. DY Patil Medical College, Navi Mumbai, India
| | - Ghasem Rahmatpour Rokni
- Department of Dermatology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Samira Beyzaee
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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9
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Yang Z, Wei F, Zhang B, Luo Y, Xing X, Wang M, Chen R, Sun G, Sun X. Cellular Immune Signal Exchange From Ischemic Stroke to Intestinal Lesions Through Brain-Gut Axis. Front Immunol 2022; 13:688619. [PMID: 35432368 PMCID: PMC9010780 DOI: 10.3389/fimmu.2022.688619] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 03/16/2022] [Indexed: 12/24/2022] Open
Abstract
As a vital pivot for the human circulatory system, the brain-gut axis is now being considered as an important channel for many of the small immune molecules’ transductions, including interleukins, interferons, neurotransmitters, peptides, and the chemokines penetrating the mesentery and blood brain barrier (BBB) during the development of an ischemic stroke (IS). Hypoxia-ischemia contributes to pituitary and neurofunctional disorders by interfering with the molecular signal release and communication then providing feedback to the gut. Suffering from such a disease on a long-term basis may cause the peripheral system’s homeostasis to become imbalanced, and it can also lead to multiple intestinal complications such as gut microbiota dysbiosis (GMD), inflammatory bowel disease (IBD), necrotizing enterocolitis (NEC), and even the tumorigenesis of colorectal carcinoma (CRC). Correspondingly, these complications will deteriorate the cerebral infarctions and, in patients suffering with IS, it can even ruin the brain’s immune system. This review summarized recent studies on abnormal immunological signal exchange mediated polarization subtype changes, in both macrophages and microglial cells as well as T-lymphocytes. How gut complications modulate the immune signal transduction from the brain are also elucidated and analyzed. The conclusions drawn in this review could provide guidance and novel strategies to benefit remedies for both IS and relative gut lesions from immune-prophylaxis and immunotherapy aspects.
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Affiliation(s)
- Zizhao Yang
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
| | - Fei Wei
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bin Zhang
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yun Luo
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoyan Xing
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Min Wang
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Rongchang Chen
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Guibo Sun
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Guibo Sun, ; Xiaobo Sun,
| | - Xiaobo Sun
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Guibo Sun, ; Xiaobo Sun,
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10
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Jadeja SD, Vaishnav J, Bharti AH, Begum R. Elevated X-Box Binding Protein1 Splicing and Interleukin-17A Expression Are Associated With Active Generalized Vitiligo in Gujarat Population. Front Immunol 2022; 12:801724. [PMID: 35046957 PMCID: PMC8761938 DOI: 10.3389/fimmu.2021.801724] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 12/13/2021] [Indexed: 11/18/2022] Open
Abstract
Vitiligo is an autoimmune skin disorder defined by the destruction of functional epidermal melanocytes. It is a multifactorial and polygenic disorder caused due to oxidative stress, endoplasmic reticulum (ER) stress, and autoimmunity, among other factors. In the present study, we aimed to investigate the association of X-box Binding Protein 1 (XBP1) and Interleukin-17A (IL-17A) polymorphisms and monitor their systemic as well as skin expression levels in vitiligo patients from Gujarat population in India. XBP1 rs2269577 G/C, IL17A rs2275913 G/A and IL17A rs8193036 C/T polymorphisms were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method in 312 controls and 276 vitiligo patients. Transcript levels of spliced (sXBP1), unspliced XBP1 (uXBP1) and IL17A from peripheral blood mononuclear cells (PBMCs) as well as spliced and unspliced XBP1 from skin samples were analyzed by qPCR. IL-17A protein levels in suction-induced blister fluid (SBF) from the skin of study subjects were estimated by ELISA. The results revealed that genotype (p=0.010) and allele (p=0.014) frequencies of XBP1 rs2269577 G/C polymorphism were significantly different, however, no significant difference was observed in frequencies of IL17A rs2275913 G/A and IL17A rs8193036 C/T polymorphisms in control and patient population. Gene expression analysis revealed that sXBP1 and IL17A levels were significantly higher in PBMCs of generalized (p=0.030 and p=0.039, respectively) and active (p=0.024 and p=0.017, respectively) vitiligo patients. Moreover, we observed a significantly elevated sXBP1 expression (p=0.037) as well as IL-17A protein levels (p=0.009) in perilesional skin of vitiligo patients as compared to controls. Overall, these findings suggest XBP1 and IL17A play an important role in vitiligo and further substantiate the involvement of ER stress in exacerbating immune-mediated vitiligo pathogenesis.
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Affiliation(s)
- Shahnawaz D Jadeja
- Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
| | - Jayvadan Vaishnav
- Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
| | - Ankit H Bharti
- Dermatology Department, Dr. Ankit's Dermatopathology Research Centre, Vyara, India
| | - Rasheedunnisa Begum
- Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India
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11
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Saleh AA, Shehata WA, Abd-Elhafiz HI, Soliman SE. Potential impact of TNFAIP3 rs6920220 and DEFB1 rs1800972 gene polymorphisms on vitiligo in Egyptian patients. Meta Gene 2022. [DOI: 10.1016/j.mgene.2021.101002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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12
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Faraj S, Kemp EH, Gawkrodger DJ. Patho-immunological mechanisms of vitiligo: the role of the innate and adaptive immunities and environmental stress factors. Clin Exp Immunol 2022; 207:27-43. [PMID: 35020865 PMCID: PMC8802175 DOI: 10.1093/cei/uxab002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 10/04/2021] [Accepted: 10/15/2021] [Indexed: 12/17/2022] Open
Abstract
Epidermal melanocyte loss in vitiligo, triggered by stresses ranging from trauma to emotional stress, chemical exposure or metabolite imbalance, to the unknown, can stimulate oxidative stress in pigment cells, which secrete damage-associated molecular patterns that then initiate innate immune responses. Antigen presentation to melanocytes leads to stimulation of autoreactive T-cell responses, with further targeting of pigment cells. Studies show a pathogenic basis for cellular stress, innate immune responses and adaptive immunity in vitiligo. Improved understanding of the aetiological mechanisms in vitiligo has already resulted in successful use of the Jak inhibitors in vitiligo. In this review, we outline the current understanding of the pathological mechanisms in vitiligo and locate loci to which therapeutic attack might be directed.
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Affiliation(s)
- Safa Faraj
- Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | | | - David John Gawkrodger
- Department of Infection, Immunology and Cardiovascular Disease, University of Sheffield, Sheffield, UK
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Zhang JZ, Abudoureyimu D, Wang M, Yu SR, Kang XJ. Association between celiac disease and vitiligo: A review of the literature. World J Clin Cases 2021; 9:10430-10437. [PMID: 35004975 PMCID: PMC8686139 DOI: 10.12998/wjcc.v9.i34.10430] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 06/25/2021] [Accepted: 10/20/2021] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is an autoimmune intestinal disease caused by the intake of gluten-containing cereals and their products by individuals with genetic susceptibility genes. Vitiligo is a commonly acquired depigmentation of the skin; its clinical manifestation are skin patches caused by localized or generalized melanin deficiency. Both diseases have similar global incidence rates (approximately 1%) and are associated to similar diseases, including autoimmune bullous disease, inflammatory bowel disease, autoimmune thyroiditis, autoimmune gastritis, and type 1 diabetes. The relationship between CD and vitiligo has been reported in several studies, but their conclusions are inconsistent. Further, it has also been reported that a gluten-free diet (GFD) can improve the symptoms of immune-related skin diseases such as vitiligo. In this mini-review, we summarize and review the literature on the relationship between CD and vitiligo, assess the therapeutic significance of GFD for patients with vitiligo, and explore their possible physiopathology. We are hopeful that the information summarized here will assist physicians who treat patients with CD or vitiligo, thereby improving the prognosis.
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Affiliation(s)
- Jing-Zhan Zhang
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Key Laboratory of Dermatology Research, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Dilinuer Abudoureyimu
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Key Laboratory of Dermatology Research, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Man Wang
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Shi-Rong Yu
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Key Laboratory of Dermatology Research, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Xiao-Jing Kang
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Key Laboratory of Dermatology Research, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
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14
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Zhao SJ, Jia H, Xu XL, Bu WB, Zhang Q, Chen X, Ji J, Sun JF. Identification of the Role of Wnt/β-Catenin Pathway Through Integrated Analyses and in vivo Experiments in Vitiligo. Clin Cosmet Investig Dermatol 2021; 14:1089-1103. [PMID: 34511958 PMCID: PMC8423189 DOI: 10.2147/ccid.s319061] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 07/14/2021] [Indexed: 01/18/2023]
Abstract
Purpose Vitiligo is an acquired depigmentation skin disease, which affects an average of 1% of the world’s population. The purpose of this study is to identify the key genes and pathways responsible for vitiligo and find new therapeutic targets. Methods The datasets GSE65127, GSE53146, and GSE75819 were downloaded from the Gene Expression Omnibus (GEO) database. R language was used to identify the differentially expressed genes (DEGs) between lesional skin of vitiligo and non-lesional skin. Next, the key pathways were obtained by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The protein–protein interaction (PPI) networks were conducted by STRING database and Cytoscape software. Subsequently, module analysis was performed by Cytoscape. Among these results, the Wnt/β-catenin pathway and melanogenesis pathway caught our attention. The expression level of β-catenin, microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) was detected by immunofluorescence in vitiligo lesions and healthy skin. Moreover, zebrafish was treated with XAV-939, an inhibitor of the Wnt/β-catenin pathway. After that, the area of melanin granules as a percentage of the head area was measured. The mRNA expression of β-catenin, lymphoid-enhancing factor 1(lef1), tyr and mitf were detected by q-PCR (quantitative polymerase chain reaction) in zebrafish (Danio rerio). Results A total of 2442 DEGs were identified, including 1068 upregulated and 1374 downregulated DEGs. The key pathways were identified by GO and KEGG analyses, such as “NOD-like receptor signaling pathway”, “Wnt signaling pathway”, “Melanogenesis”, “mTOR signaling pathway”, “PI3K-Akt signaling pathway”, “Calcium signaling pathway” and “Rap1 signaling pathway”. The immunofluorescence results showed that the level of β-catenin, MITF and TYR was significantly downregulated in vitiligo lesional skin. In zebrafish, the mean percentage area of melanin granules and the expression of β-catenin, lef1, tyr and mitf were decreased after treated with XAV-939. Conclusion The present study identified key genes and signaling pathways associated with the pathophysiology of vitiligo. Among them, the Wnt/β-catenin pathway played an essential role in pigmentation and could be a breakthrough point in vitiligo treatment.
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Affiliation(s)
- Si-Jia Zhao
- Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, People's Republic of China
| | - Hong Jia
- Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, People's Republic of China
| | - Xiu-Lian Xu
- Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, People's Republic of China
| | - Wen-Bo Bu
- Department of Dermatologic Surgery, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, People's Republic of China
| | - Qian Zhang
- Department of Dermatologic Surgery, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, People's Republic of China
| | - Xi Chen
- Department of Medicine 3, Universitätsklinikum Erlangen, Friedrich Alexander University Erlangen Nuremberg, Erlangen, Bavaria, Germany
| | - Juan Ji
- Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, People's Republic of China
| | - Jian-Fang Sun
- Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, People's Republic of China
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15
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Alhelf M, Rashed LA, Ragab N, Elmasry MF. Association between long noncoding RNA taurine-upregulated gene 1 and microRNA-377 in vitiligo. Int J Dermatol 2021; 61:199-207. [PMID: 34014568 DOI: 10.1111/ijd.15669] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 03/15/2021] [Accepted: 04/22/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND Taurine-upregulated gene 1 (TUG1) is one of the long noncoding RNAs (lncRNAs) that plays a role in melanogenesis. MicroRNA-377 (miRNA-377) is a conserved noncoding RNA that regulates angiogenesis and promotes oxidative stress. Peroxisome proliferator-activated receptors (PPARs) are components of the nuclear hormone receptor superfamily. PPAR-γ activators stimulate melanogenesis. Interleukin (IL)-17 has been implicated in the pathogenesis of several immunological diseases. This work aimed at detecting the expression levels of lncRNA TUG1, miRNA-377, PPAR-γ, and IL-17 among vitiligo subjects and to investigate their possible role in the pathogenesis of vitiligo. METHODS This study was conducted on 30 healthy controls and 30 vitiligo patients. LncRNA TUG1 and miRNA-377 were detected in serum by real-time polymerase chain reaction (PCR). Also, expressions of PPAR-γ and IL-17 were assessed in tissue by real-time PCR. RESULTS LncRNA TUG1 and PPAR-γ levels were significantly downregulated in the vitiligo group compared with the control group. On the other hand, miRNA-377 and IL-17 were significantly upregulated in the vitiligo group compared with the control group. CONCLUSION This study demonstrated the dysregulated expressions of lncRNA TUG1 and miRNA-377 in patients with vitiligo suggesting that both contributed to the pathogenesis of vitiligo that might be through PPAR-γ downregulation and IL-17 upregulation.
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Affiliation(s)
- Maha Alhelf
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.,Biotechnology School, Nile University, Giza, Egypt
| | - Laila A Rashed
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Noura Ragab
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Maha F Elmasry
- Dermatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Increased Circulatory Interleukin-17A Levels in Patients with Progressive and Leukotrichial Vitiligo. Dermatol Res Pract 2021; 2021:5524566. [PMID: 33968147 PMCID: PMC8084637 DOI: 10.1155/2021/5524566] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 03/28/2021] [Accepted: 04/05/2021] [Indexed: 11/18/2022] Open
Abstract
Background Vitiligo is a chronic condition characterized by skin depigmentation. Although not life-threatening, it significantly impacts quality of life. The pathophysiology of vitiligo remains poorly understood, and treatment options are limited. Mounting evidence supports the importance of autoreactive T cells and, particularly interleukin-17A- (IL-17A-) secreting Th17 cells, in vitiligo. IL-17A targeting has been proven successful in various inflammatory dermatological conditions, including psoriasis and lupus erythematosus. Objective We evaluated the relationship between serum levels of IL-17A and the clinicopathological characteristics of Vietnamese vitiligo patients. Methods In this cross-sectional study, we analyzed data from 52 nonsegmental vitiligo patients and 50 age- and sex-matched healthy individuals. Serum levels of IL-17A were measured using an enzyme-linked immunosorbent assay. We evaluated the correlation between IL-17A levels and clinical characteristics including leukotrichia, disease duration, vitiligo activity, and body surface area involvement. Results Patients with progressive vitiligo had significantly higher IL-17A levels than patients with stable vitiligo (P = 0.014) or healthy individuals (P = 0.002). In addition, serum IL-17A levels were higher in vitiligo patients with leukotrichia than in patients without it (P = 0.04). Furthermore, serum IL-17A levels were negatively correlated with age (r = -0.39, P = 0.004) and age of onset (r = -0.33, P = 0.016) in vitiligo patients. Conclusions Higher serum levels of IL-17A in patients with progressive vitiligo and leukotrichia suggest a potential role of IL-17A in melanocyte destruction in the epidermis and the follicular matrix.
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17
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Hung CT, Huang HH, Wang CK, Chung CH, Tsao CH, Chien WC, Wang WM. Pregnancy outcomes in women with vitiligo: A Taiwanese nationwide cohort study. PLoS One 2021; 16:e0248651. [PMID: 33750961 PMCID: PMC7984608 DOI: 10.1371/journal.pone.0248651] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 03/02/2021] [Indexed: 12/27/2022] Open
Abstract
Vitiligo is perceived as an autoimmune skin disease. Previous studies showed conflicting data about vitiligo and pregnancy outcomes. To delineate the associations between vitiligo and the pregnancy outcomes, we used the National Health Insurance Research Database of Taiwan to conduct a retrospective cohort study from January 1, 2000 to December 31, 2015. This study population was composed of 1,096 women with vitiligo and 4,384 women without vitiligo, who were all matched according to age, comorbidity, and index year. Compared with the non-vitiligo controls, women with vitiligo had a higher risk of abortion (aHR 1.158, 95% confidence interval (CI) 1.095–1.258, P < .001). Perinatal events, such as preterm delivery, pre-eclampsia/eclampsia, gestational diabetes mellitus, stillbirth, and intrauterine growth retardation, were not different between both groups (aHR 1.065, 95% CI 0.817–1.157, P = .413). To determine if systemic treatment before conception decreases the risk of abortion, we assessed the medical history of pregnant women with vitiligo 1 year before pregnancy. Patients who were treated with oral medications had a lower risk of abortion than those who were not (aHR: 0.675, 95% CI: 0.482–0.809, P < .001). Our study indicates that there is a higher risk of abortion in pregnant women with vitiligo and the control of disease activity with systemic treatment before conception could improve pregnancy outcomes.
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Affiliation(s)
- Chih-Tsung Hung
- Department of Dermatology, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan
- National Defense Medical Center, Graduate Institute of Medical Sciences, Taipei, Taiwan
| | - Hsin-Hui Huang
- Department of Obstetrics and Gynecology, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan
| | - Chun-Kai Wang
- Department of Obstetrics and Gynecology, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | - Chi-Hsiang Chung
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Taiwanese Injury Prevention and Safety Promotion Association, Taipei, Taiwan
| | - Chang-Huei Tsao
- Department of Medical Research, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan
- Department of Microbiology & Immunology, National Defense Medical Center, Taipei, Taiwan
| | - Wu-Chien Chien
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
- Department of Medical Research, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan
- * E-mail: (WC); (WW)
| | - Wei-Ming Wang
- Department of Dermatology, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan
- National Defense Medical Center, Graduate Institute of Medical Sciences, Taipei, Taiwan
- * E-mail: (WC); (WW)
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18
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Chen J, Li S, Li C. Mechanisms of melanocyte death in vitiligo. Med Res Rev 2021; 41:1138-1166. [PMID: 33200838 PMCID: PMC7983894 DOI: 10.1002/med.21754] [Citation(s) in RCA: 135] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 10/16/2020] [Accepted: 11/01/2020] [Indexed: 12/12/2022]
Abstract
Vitiligo is an autoimmune depigment disease results from extensive melanocytes destruction. The destruction of melanocyte is thought to be of multifactorial causation. Genome-wide associated studies have identified single-nucleotide polymorphisms in a panel of susceptible loci as risk factors in melanocyte death. But vitiligo onset can't be solely attributed to a susceptive genetic background. Oxidative stress triggered by elevated levels of reactive oxygen species accounts for melanocytic molecular and organelle dysfunction, a minority of melanocyte demise, and melanocyte-specific antigens exposure. Of note, the self-responsive immune function directly contributes to the bulk of melanocyte deaths in vitiligo. The aberrantly heightened innate immunity, type-1-skewed T helper, and incompetent regulatory T cells tip the balance toward autoreaction and CD8+ cytotoxic T lymphocytes finally execute the killing of melanocytes, possibly alarmed by resident memory T cells. In addition to the well-established apoptosis and necrosis, we discuss several death modalities like oxeiptosis, ferroptosis, and necroptosis that are probably employed in melanocyte destruction. This review focuses on the various mechanisms of melanocytic death in vitiligo pathogenesis to demonstrate a panorama of that. We hope to provide new insights into vitiligo pathogenesis and treatment strategies by the review.
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Affiliation(s)
- Jianru Chen
- Department of DermatologyXijing hospital, Fourth Military Medical UniversityXi'anShannxiChina
| | - Shuli Li
- Department of DermatologyXijing hospital, Fourth Military Medical UniversityXi'anShannxiChina
| | - Chunying Li
- Department of DermatologyXijing hospital, Fourth Military Medical UniversityXi'anShannxiChina
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19
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Montamat G, Leonard C, Poli A, Klimek L, Ollert M. CpG Adjuvant in Allergen-Specific Immunotherapy: Finding the Sweet Spot for the Induction of Immune Tolerance. Front Immunol 2021; 12:590054. [PMID: 33708195 PMCID: PMC7940844 DOI: 10.3389/fimmu.2021.590054] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 01/04/2021] [Indexed: 01/16/2023] Open
Abstract
Prevalence and incidence of IgE-mediated allergic diseases have increased over the past years in developed and developing countries. Allergen-specific immunotherapy (AIT) is currently the only curative treatment available for allergic diseases that has long-term efficacy. Although AIT has been proven successful as an immunomodulatory therapy since its beginnings, it still faces several unmet needs and challenges today. For instance, some patients can experience severe side effects, others are non-responders, and prolonged treatment schedules can lead to lack of patient adherence and therapy discontinuation. A common strategy to improve AIT relies on the use of adjuvants and immune modulators to boost its effects and improve its safety. Among the adjuvants tested for their clinical efficacy, CpG oligodeoxynucleotide (CpG-ODN) was investigated with limited success and without reaching phase III trials for clinical allergy treatment. However, recently discovered immune tolerance-promoting properties of CpG-ODN place this adjuvant again in a prominent position as an immune modulator for the treatment of allergic diseases. Indeed, it has been shown that the CpG-ODN dose and concentration are crucial in promoting immune regulation through the recruitment of pDCs. While low doses induce an inflammatory response, high doses of CpG-ODN trigger a tolerogenic response that can reverse a pre-established allergic milieu. Consistently, CpG-ODN has also been found to stimulate IL-10 producing B cells, so-called B regulatory cells (Bregs). Accordingly, CpG-ODN has shown its capacity to prevent and revert allergic reactions in several animal models showing its potential as both preventive and active treatment for IgE-mediated allergy. In this review, we describe how CpG-ODN-based therapies for allergic diseases, despite having shown limited success in the past, can still be exploited further as an adjuvant or immune modulator in the context of AIT and deserves additional attention. Here, we discuss the past and current knowledge, which highlights CpG-ODN as a potential adjuvant to be reevaluated for the enhancement of AIT when used in appropriate conditions and formulations.
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Affiliation(s)
- Guillem Montamat
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.,Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Cathy Leonard
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | - Aurélie Poli
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | - Ludger Klimek
- Centre for Rhinology and Allergology, Wiesbaden, Germany
| | - Markus Ollert
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg.,Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark
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20
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Abstract
OBJECTIVES Vitiligo is an autoimmune disease, and its pathogenesis involves changes in cytokine levels in the affected patients. Tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-17 from pro-inflammatory cytokines, IL-37 in a recently detected anti-inflammatory activity. The aim of our study was to determine serum TNF-α, IL-6, IL-17, IL-37 levels in patients with vitiligo to understand their possible roles in the disease etiology and to compare the results with the healthy controls. METHODS The study included 48 generalized vitiligo patients who were diagnosed with vitiligo, had an increase in the lesions within the last 3 months, and did not receive any systemic or topical treatment during this period; furthermore, 18 healthy controls were included. RESULTS Patient group: n = 48, mean age = 30.48 ± 9.86 years; control group: n = 18, mean age = 28.27 ± 9.66 years. Individuals in the patient group had significantly higher serum levels of IL-37(t = 3.90, p < .001), IL-6 (t = 3.39, p < .05), IL-17 (t = 2.08, p < .05), and TNF-α (t = 4.69 p < .001) than in the control group. CONCLUSION The high levels of (pro-anti) inflammatory cytokines in vitiligo patients draw attention to the importance of cytokines in the pathogenesis of the disease.
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Affiliation(s)
- Ebru Karagün
- Department of Dermatology, Duzce University Medical School, Duzce, Turkey
| | - Sevim Baysak
- Department of Dermatology, Istanbul Sultan Abdülhamid Han Training and Research Hospital, Istanbul, Turkey
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21
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Aghamajidi A, Raoufi E, Parsamanesh G, Jalili A, Salehi-Shadkami M, Mehrali M, Mohsenzadegan M. The attentive focus on T cell-mediated autoimmune pathogenesis of psoriasis, lichen planus and vitiligo. Scand J Immunol 2020; 93:e13000. [PMID: 33190330 DOI: 10.1111/sji.13000] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Revised: 09/16/2020] [Accepted: 11/10/2020] [Indexed: 12/14/2022]
Abstract
T cell-mediated autoimmune skin diseases develop as a result of the aberrant immune response to the skin cells with T cells playing a central role. These chronic inflammatory skin diseases encompass various types including psoriasis, lichen planus and vitiligo. These diseases show similarities in their immune-pathophysiology. In the last decade, immunomodulating agents have been very successful in the management of these diseases thanks to a better understanding of the pathophysiology. In this review, we will discuss the immunopathogenic mechanisms and highlight the role of T lymphocytes in psoriasis, lichen planus and vitiligo. This study could provide new insights into a better understanding of targeted therapeutic pathways and biological therapies.
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Affiliation(s)
- Azin Aghamajidi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ehsan Raoufi
- Department of Medical Biotechnology, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Gilda Parsamanesh
- Department of Immunology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Ahmad Jalili
- Dermatology & Skin Care, Buergenstock Medical Center, Obbuergen, Switzerland
| | - Mohammad Salehi-Shadkami
- Student Research Committee, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Marjan Mehrali
- Student Research Committee, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Monireh Mohsenzadegan
- Department of Medical Laboratory Science, Faculty of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
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22
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The Role of T RM Cells in the Pathogenesis of Vitiligo-A Review of the Current State-Of-The-Art. Int J Mol Sci 2020; 21:ijms21103552. [PMID: 32443482 PMCID: PMC7278984 DOI: 10.3390/ijms21103552] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 05/08/2020] [Accepted: 05/10/2020] [Indexed: 12/12/2022] Open
Abstract
Vitiligo is the most common hypopigmentation disease affecting both the skin and mucous membranes. The pathogenesis of this disorder is complex and involves the influence of genetic and environmental factors, oxidative stress, and autoimmune responses. Recent studies have indicated that skin lesions observed in vitiligo tend to recur in the same places where they were found before treatment. This phenomenon is explained by the presence of recently discovered tissue-resident memory T cells (TRM), whose primary function is to provide antiviral and antibacterial protection in non-lymphoid tissues. TRM cells show the presence of CD49a, CD69, and CD103 markers on their surface, although not all of them express these particles. Due to their ability to produce and secrete perforin, IFN-γ, and granzyme B, TRM cells demonstrate a cytotoxic effect on melanocytes, thus inducing depigmented lesions in the course of the vitiligo. It has been proved that the occurrence of TRM cells largely depends on IL-15, which promotes the TRM function ex vivo. The findings above, as well as their reference to the pathogenesis of autoimmune skin diseases will have a considerable influence on the development of new therapeutic strategies in the near future. This article presents an up-to-date review of information regarding the role of TRM cells in the development and progression of vitiligo.
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23
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Zhao G, Zhou W, Liu Y, Wang Y, Li Z, Song Z. Critical role of metabotropic glutamate receptor 4 in bone marrow-derived dendritic cells in the Th17 cell differentiation and the melanogenesis of B16 cells. ACTA ACUST UNITED AC 2020; 53:e9282. [PMID: 32267311 PMCID: PMC7162588 DOI: 10.1590/1414-431x20209282] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Accepted: 01/13/2020] [Indexed: 12/15/2022]
Abstract
Vitiligo is an acquired pigmentary disorder resulting from selective destruction of melanocytes. Emerging studies have suggested that T helper cell 17 (Th17) is potentially implicated in vitiligo development and progression. It was recently discovered that metabotropic glutamate receptor 4 (mGluR4) can modulate Th17-mediated adaptive immunity. However, the influence of mGluR4 on melanogenesis of melanocytes has yet to be elucidated. In the present study, we primarily cultured mouse bone marrow-derived dendritic cells (BMDC) and then knocked down and over-expressed mGluR4 using transfection. Transduced BMDC were co-cultured with CD4+ T cells and the expression of Th17-related cytokines were measured. The morphology and melanogenesis of B16 cells were observed after being treated with co-culture medium of CD4+ T cells and transduced BMDC. We found that mGluR4 knockdown did not affect the co-stimulatory CD80 and CD86 upregulation after lipopolysaccharide stimulation but did increase the expression of Th17-related cytokines, and further down-regulated the expression of microphthalmia-associated transcription factor (MITF) and the downstream genes, decreased melanin production, and destroyed the morphology of B16 cells. Conversely, over-expression of mGluR4 reduced the expression of CD80 and CD86, suppressed the production of Th17-related cytokines, increased the expression of MITF, and did not destroy the morphology of B16 cells. Our study confirmed that mGluR4 modulated the Th17 cell polarization and resulted in the alteration of melanogenesis and morphology of B16 cells. Collectively, these findings suggest mGluR4 might be a potent target involved in the immune pathogenesis of vitiligo.
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Affiliation(s)
- Guangming Zhao
- Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Wenhui Zhou
- Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Ying Liu
- Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Yupeng Wang
- Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Zhou Li
- Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Zhiqi Song
- Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
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24
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Biswas KB, Takahashi A, Mizutani Y, Takayama S, Ishitsuka A, Yang L, Yang F, Iddamalgoda A, Katayama I, Inoue S. GPNMB is expressed in human epidermal keratinocytes but disappears in the vitiligo lesional skin. Sci Rep 2020; 10:4930. [PMID: 32188902 PMCID: PMC7080742 DOI: 10.1038/s41598-020-61931-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 03/03/2020] [Indexed: 12/11/2022] Open
Abstract
GPNMB is involved in multiple cellular functions including cell adhesion, stress protection and stem cell maintenance. In skin, melanocyte-GPNMB is suggested to mediate pigmentation through melanosome formation, but details of keratinocyte-GPNMB have yet to be well understood. We confirmed the expression of GPNMB in normal human epidermal keratinocytes (NHEKs) by reducing the expression using siRNA. A higher calcium concentration of over 1.25 mM decreased the GPNMB expression. Histological staining showed that GPNMB was expressed in the basal layer of normal skins but completely absent in vitiligo skins. The normal expression of GPNMB in nevus depigmentosus skin suggested that lack of GPNMB is characteristic of vitiligo lesional skins. IFN-γ and IL-17A, two cytokines with possible causal roles in vitiligo development, inhibited GPNMB expression in vitro. Approximately 4–8% of the total GPNMB expressed on NHEKs were released possibly by ADAM 10 as a soluble form, but the process of release was not affected by the cytokines. The suppressive effect of IFN-γ on GPNMB was partially via IFN-γ/JAK2/STAT1 signaling axis. Decreased GPNMB expression in keratinocytes may affect melanocyte maintenance or survival against oxidative stress although further studies are needed. These findings indicate a new target for vitiligo treatment, focusing on the novel role of IFN-γ and IL-17 in downregulating keratinocyte-GPNMB.
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Affiliation(s)
- Kazal Boron Biswas
- Department of Cosmetic Health Science, Gifu Pharmaceutical University, Gifu, Japan.,Department of Research and Development, Ichimaru Pharcos Co. Ltd., Motosu, Gifu, Japan
| | - Aya Takahashi
- Department of Dermatology, Osaka University School of Medicine, Osaka, Japan
| | - Yukiko Mizutani
- Department of Cosmetic Health Science, Gifu Pharmaceutical University, Gifu, Japan
| | - Satoru Takayama
- Department of Cosmetic Health Science, Gifu Pharmaceutical University, Gifu, Japan.,Department of Research and Development, Ichimaru Pharcos Co. Ltd., Motosu, Gifu, Japan
| | - Asako Ishitsuka
- Department of Cosmetic Health Science, Gifu Pharmaceutical University, Gifu, Japan
| | - Lingli Yang
- Department of Dermatology, Osaka University School of Medicine, Osaka, Japan
| | - Fei Yang
- Department of Dermatology, Osaka University School of Medicine, Osaka, Japan
| | - Arunasiri Iddamalgoda
- Department of Cosmetic Health Science, Gifu Pharmaceutical University, Gifu, Japan.,Department of Research and Development, Ichimaru Pharcos Co. Ltd., Motosu, Gifu, Japan
| | - Ichiro Katayama
- Department of Dermatology, Osaka University School of Medicine, Osaka, Japan.
| | - Shintaro Inoue
- Department of Cosmetic Health Science, Gifu Pharmaceutical University, Gifu, Japan.
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Martins C, Darrigade AS, Jacquemin C, Barnetche T, Taieb A, Ezzedine K, Boniface K, Seneschal J. Phenotype and function of circulating memory T cells in human vitiligo. Br J Dermatol 2020; 183:899-908. [PMID: 32012221 DOI: 10.1111/bjd.18902] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/30/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Vitiligo is a chronic inflammatory skin disorder characterized by the loss of melanocytes. While a T helper cell (Th)1/cytotoxic T cell (Tc)1-skewed immune response is now well demonstrated in vitiligo, recent data suggest that the T-cell component could be more complex, involving different combinatorial T-cell subsets. OBJECTIVES To analyse the phenotype and function of circulating CD4+ and CD8+ memory T-cell subsets in patients with stable and active vitiligo, in comparison with patients with psoriasis and healthy controls. METHODS This is a monocentric, prospective, descriptive and exploratory study. Multiparametric flow cytometry analyses were performed to evaluate the surface expression of homing and T-cell-subset markers together with intracellular cytokine production in peripheral blood mononuclear cells from 60 patients with vitiligo, 25 patients with psoriasis and 28 healthy donors. RESULTS Vitiligo peripheral blood circulating effector and central memory T cells expressed similar proportions of skin-homing markers. Decrease in the frequencies of circulating CD4+ and CD8+ Th1/Tc1, Th17/Tc17, and Th1/Th17 or Tc1/Tc17 effector memory T-cell subsets were observed in patients with vitiligo compared with healthy donors. Similar observations were made in psoriasis. In contrast, vitiligo circulating T cells showed a similar capacity for proinflammatory cytokine production compared with those in psoriasis and healthy controls. CONCLUSIONS The decreased frequencies of circulating Th1/Tc1, Th17/Tc17 and Th1/Th17-Tc1/Tc17 cells suggest a possible migration of these T-cell subsets into the skin of patients with vitiligo. These could be targeted to prevent flares of the disease. What is already known about this topic? Vitiligo is a chronic inflammatory skin disorder associated with the loss of melanocytes. Vitiligo is characterized by a T helper cell (Th)1/cytotoxic T cell (Tc)1-skewed immune response in the skin. What does this study add? A thorough analysis of the phenotype and function of circulating memory T cells suggests the migration of Th1/Tc1, Th17/Tc17 and Th1/Th17-Tc1/Tc17 cell subsets in the skin. What is the translational message? A better understanding of the different immune T-cell subsets involved in vitiligo could lead to better therapeutic options. Linked Comment: Matos. Br J Dermatol 2020; 183:803.
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Affiliation(s)
- C Martins
- INSERM U1035, BMGIC, Immuno-Dermatology Team, University of Bordeaux, Bordeaux, France
| | - A-S Darrigade
- INSERM U1035, BMGIC, Immuno-Dermatology Team, University of Bordeaux, Bordeaux, France.,Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, Bordeaux, France
| | - C Jacquemin
- INSERM U1035, BMGIC, Immuno-Dermatology Team, University of Bordeaux, Bordeaux, France
| | - T Barnetche
- Department of Rheumatology, National Reference Center for Severe Systemic Auto-Immune Diseases, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France
| | - A Taieb
- INSERM U1035, BMGIC, Immuno-Dermatology Team, University of Bordeaux, Bordeaux, France.,Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, Bordeaux, France
| | - K Ezzedine
- Department of Dermatology, AP-HP, Hôpital Henri-Mondor, Créteil, France
| | - K Boniface
- INSERM U1035, BMGIC, Immuno-Dermatology Team, University of Bordeaux, Bordeaux, France.,Fédération Hospitalo-Universitaire, ACRONIM, Bordeaux, France
| | - J Seneschal
- INSERM U1035, BMGIC, Immuno-Dermatology Team, University of Bordeaux, Bordeaux, France.,Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, Bordeaux, France.,Fédération Hospitalo-Universitaire, ACRONIM, Bordeaux, France
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26
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Bhardwaj S, Rani S, Kumaran MS, Bhatia A, Parsad D. Expression of Th17- and Treg-specific transcription factors in vitiligo patients. Int J Dermatol 2020; 59:474-481. [PMID: 31909498 DOI: 10.1111/ijd.14766] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 11/04/2019] [Accepted: 12/09/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND Vitiligo is mainly considered an autoimmune skin disease as the number of IL-17 producing Th17 cells, involved in the development of autoimmune and inflammatory pathologies, increased in vitiligo skin. T regulatory cells (Tregs) seem to be altered during the disease. Thus, there must be some upstream molecular factors that regulate the cellular response to apoptotic and inflammatory stimuli. OBJECTIVES To investigate the expression of Th17- and Treg-specific transcription factors in PBMCs and to evaluate the correlation between these transcription factors and cytokines in vitiligo patients. METHODS We investigated 30 active NSV patients for Th17- and Treg-specific transcription factors RORγt (retinoic acid-related orphan receptor gamma t), FOXP3 (forkhead/winged helix), HELIOS, EOS, and IRF4 (Interferon Regulatory Factor 4) as well as apoptotic marker NALP1 (NACHT-leucine-rich-repeat protein 1) in PBMCs with RT-qPCR. Immunostaining was done for transcription factors and cytokines on skin sections. RESULTS The mRNA level of FOXP3 was significantly lower in patients (0.76 fold, P < 0.001), whereas RORγt was slight but not significantly increased (0.76 fold, P = 0.06). Furthermore, NALP1 in lymphocytes was found to be increased in patients (0.69 fold, P < 0.01). The immunostaining results revealed increased expression of RORγ, IL-17A, NALP1, and IL-1β in vitiligo skin when compared to normal healthy skin. CONCLUSION Reduced FOXP3/RORγt mRNA ratio suggests thriving of the Th17 cell population in PBMCs of vitiligo patients. Increased NALP1 levels indicate the existence of an apoptotic phenomenon which correlates with the increased expression of IL-1β in vitiligo pathogenesis.
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Affiliation(s)
- Supriya Bhardwaj
- Department of Dermatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Seema Rani
- Department of Zoology, Punjab University, Chandigarh, India.,Department of Zoology, Hindu Girls College, Sonepat, India
| | - Muthu S Kumaran
- Department of Dermatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Alka Bhatia
- Department of Experimental Medicine & Biotechnology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Davinder Parsad
- Department of Dermatology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
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27
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Acharya P, Mathur M. Interleukin-17 level in patients with vitiligo: A systematic review and meta-analysis. Australas J Dermatol 2020; 61:e208-e212. [PMID: 31895472 DOI: 10.1111/ajd.13233] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/17/2019] [Accepted: 12/07/2019] [Indexed: 11/28/2022]
Abstract
BACKGROUND/OBJECTIVES The role of the pro-inflammatory cytokine, interleukin (IL)-17 is being continuously explored in various autoimmune disorders. Studies have assessed the levels of IL-17 in vitiligo patients. This study aims to evaluate the IL-17 levels in vitiligo patients in comparison with the healthy controls by performing a meta-analysis. METHODS A systematic review of the existing literature was performed in PubMed, Scopus and Cochrane databases by two authors independently. The data required to calculate the pooled effect size in the form of standardised mean difference (SMD) with the corresponding 95% confidence interval (CI) were extracted from the eligible studies. Separate analyses for active and stable vitiligo were also performed. RESULTS A total of 11 case-control studies with 626 vitiligo patients and 475 healthy controls were included. Random-effects meta-analysis found significantly higher serum IL-17 levels in vitiligo patients compared with the healthy controls (SMD = 1.67, 95% CI 1.11 to 2.22, P < 0.001). The IL-17 levels were higher in both active (SMD = 1.31, 95% CI 0.76 to 1.86) and stable (SMD = 1.47, 95% CI 0.59 to 2.35) vitiligo patients compared with the healthy controls. The skin IL-17 levels were also significantly higher in vitiligo patients (SMD = 1.28, 95% CI 0.82 to 1.74). Heterogeneity in the baseline characteristics of the included studies was the major limitation of this study. CONCLUSIONS These results suggest that vitiligo patients have significantly elevated IL-17 levels. Further examination of this association could have implications for the treatment of vitiligo.
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Affiliation(s)
- Prakash Acharya
- Department of Dermatology, College of Medical Sciences, Bharatpur, Nepal
| | - Mahesh Mathur
- Department of Dermatology, College of Medical Sciences, Bharatpur, Nepal
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28
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Li S, Kang P, Zhang W, Jian Z, Zhang Q, Yi X, Guo S, Guo W, Shi Q, Li B, He Y, Song P, Liu L, Li K, Wang G, Gao T, Li C. Activated NLR family pyrin domain containing 3 (NLRP3) inflammasome in keratinocytes promotes cutaneous T-cell response in patients with vitiligo. J Allergy Clin Immunol 2019; 145:632-645. [PMID: 31756352 DOI: 10.1016/j.jaci.2019.10.036] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 09/21/2019] [Accepted: 10/09/2019] [Indexed: 01/06/2023]
Abstract
BACKGROUND Keratinocytes can function as innate immune cells under oxidative stress and aggravate the cutaneous T-cell response that undermines melanocytes in the setting of vitiligo. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a regulator of innate immunity that exists in keratinocytes. However, the role of the NLRP3 inflammasome in the pathogenesis of vitiligo has not been investigated. OBJECTIVE We sought to explicate the contribution of the activated NLRP3 inflammasome in keratinocytes to the autoimmune response in patients with vitiligo. METHODS Perilesional and serum samples from patients with vitiligo were collected to examine the status of the NLRP3 inflammasome in the setting of vitiligo. Cultured keratinocytes were treated with H2O2 to investigate the mechanism for NLRP3 inflammasome activation under oxidative stress. Peripheral blood T cells were extracted from patients with vitiligo to explore the influence of the NLRP3 inflammasome on the T-cell response in patients with vitiligo. RESULTS Expressions of NLRP3 and downstream cytokine IL-1β were consistently increased in perilesional keratinocytes of patients with vitiligo. Notably, serum IL-1β levels were increased in patients with vitiligo, correlated with disease activity and severity, and decreased after effective therapy. Furthermore, oxidative stress promoted NLRP3 inflammasome activation in keratinocytes through transient receptor potential cation channel subfamily M member 2 (TRPM2), a redox-sensitive cation channel, which was dependent on TRPM2-mediated calcium influx. More importantly, blocking TRPM2-induced NLRP3 inflammasome activation in keratinocytes impaired chemotaxis for CD8+ T cells and inhibited the production of cytokines in T cells in patients with vitiligo. CONCLUSION Oxidative stress-induced NLRP3 inflammasome activation in keratinocytes promotes the cutaneous T-cell response, which could be targeted for the treatment of vitiligo.
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Affiliation(s)
- Shuli Li
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Pan Kang
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Weigang Zhang
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zhe Jian
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Qian Zhang
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xiuli Yi
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Sen Guo
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Weinan Guo
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Qiong Shi
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Bing Li
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yuanmin He
- Department of Dermatology, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Pu Song
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Ling Liu
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Kai Li
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Gang Wang
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Tianwen Gao
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Chunying Li
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
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Immunophenotype of circulatory T-helper cells in patients with non-segmental vitiligo. Postepy Dermatol Alergol 2019; 36:449-454. [PMID: 31616220 PMCID: PMC6791165 DOI: 10.5114/ada.2019.87448] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Accepted: 05/30/2018] [Indexed: 11/24/2022] Open
Abstract
Introduction Non-segmental vitiligo (NSV) is an immune-mediated skin depigmentation disease. Cytokine-mediated interaction between T lymphocytes and melanocytes leads to death of melanocytes, causing a defect in melanin synthesis and thereby depigmentation. There is an increased population of T-helper cells in the skin lesions as well as in the peripheral circulation in NSV. However, the relative percentage of each T-cell phenotype in the disease pathogenesis is rarely studied. Aim To study the immunophenotype of the different T-helper/Treg cell subsets in patients with NSV, in comparison to healthy controls. Material and methods A total of 80 patients with NSV and eighty age- and gender-matched healthy controls were recruited in this cross-sectional study. Disease activity was determined by vitiligo index of disease activity (VIDA) scoring. Peripheral blood mononuclear cells were separated by Ficoll-Paque density centrifugation, and T-cell immunophenotyping was done by flow cytometric analysis. Results In patients with NSV, we observed an imbalance in T-cell immunophenotype, characterized by an increase in Th1 (p < 0.0001) and Th17 cells (p = 0.01). There is no difference in relative percentage of Th2/Treg cells, as compared to the healthy controls (p > 0.05). Conclusions There is a significant immune-dysregulation with a preponderance of circulatory Th1/Th17 phenotype in NSV patients.
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30
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Das D, Akhtar S, Kurra S, Gupta S, Sharma A. Emerging role of immune cell network in autoimmune skin disorders: An update on pemphigus, vitiligo and psoriasis. Cytokine Growth Factor Rev 2019; 45:35-44. [PMID: 30773437 DOI: 10.1016/j.cytogfr.2019.01.001] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 01/18/2019] [Indexed: 12/15/2022]
Abstract
Autoimmune skin diseases are a group of disorders that arise due to a deregulated immune system resulting in skin tissue destruction. In the majority of these conditions, either autoreactive immune cells or the autoantibodies are generated against self-antigens of the skin. Although the etiology of these diseases remains elusive, biochemical, genetic, and environmental factors such as infectious agents, toxins damage the skin tissue leading to self-antigen generation, autoantibody attack and finally results in autoimmunity of skin. Immune dysregulation, which involves predominantly T helper 1/17 (Th1/Th17) polarization and the inability of regulatory T cells to regress immune response, is implicated in autoimmune skin diseases. The emerging roles of immune cells, cytokines, and chemokines in the pathogenesis of common autoimmune skin diseases like pemphigus, vitiligo, and psoriasis are discussed in this review. The main focus is on the interplay between immune cell network including the innate and adaptive immune system, regulatory cells, immune checkpoints and recently identified tissue-resident memory cells (TRMs) in disease pathogenesis and relapse. We also attempt to highlight on the immune mechanisms common to these diseases which can be targeted for designing novel therapeutics.
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Affiliation(s)
- Dayasagar Das
- Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, India
| | - Shamima Akhtar
- Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, India
| | - Santosh Kurra
- Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, India
| | - Somesh Gupta
- Department of Dermatology and Venereology, All India Institute of Medical Sciences, AIIMS, New Delhi, India
| | - Alpana Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, India.
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31
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Zhang L, Kang Y, Chen S, Wang L, Jiang M, Xiang L. Circulating CCL20: A potential biomarker for active vitiligo together with the number of Th1/17 cells. J Dermatol Sci 2019; 93:92-100. [PMID: 30655106 DOI: 10.1016/j.jdermsci.2018.12.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 12/27/2018] [Accepted: 12/28/2018] [Indexed: 11/25/2022]
Abstract
BACKGROUND Vitiligo is an autoimmune disease with varying pathological features. Activation of the CCL20-CCR6 axis plays an important role in chronic inflammatory diseases. However, whether CCL20-CCR6 and Th1/17 cells are indicative of active vitiligo is unclear. OBJECTIVE To investigate the potential role of CCL20 and the involvement of Th1/17 and Tc1/17 cells in the mechanism in vitiligo. METHODS One hundred patients with vitiligo, and 20 healthy controls were included. The serum and blister fluid IL-17, IFN-γ, CCL20, and CXCL10 were studied using enzyme-linked immunosorbent assays. The numbers of Th1/17 cells and Tc1/17 cells in circulation were quantified using flow cytometry. CCR6 mRNA in peripheral blood mononuclear cells (PBMCs) was analyzed by real-time polymerase chain reaction and the protein level was confirmed by western blotting. CCR6 and CCL20 expression in lesions was analyzed by immunohistochemistry. RESULTS The serum CCL20 level was significantly elevated in patients with vitiligo. The level of serum CCL20 was higher in active than in the stable stage, which correlated positively with the Vitiligo European Task Force spreading score and the Vitiligo Area Scoring Index score. Patients with active vitiligo had elevated numbers of circulating Th1/17 cells and Tc1/17 cells, and upregulated expression of CCR6 in PBMCs and lesions. After effective treatment, the level of CCL20 in sera and blister fluid was significantly decreased, as were the numbers of circulating Th1/17 cells and Tc1/17 cells. CONCLUSION CCL20 might be a vital biomarker of active vitiligo, and circulating Th1/17 and Tc1/17 cells are involved in the pathogenesis of vitiligo.
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Affiliation(s)
- Li Zhang
- Department of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, PR China
| | - Yuli Kang
- Department of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, PR China
| | - Shujun Chen
- Department of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, PR China
| | - Li Wang
- Department of Laboratory Medicine, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, PR China
| | - Min Jiang
- Department of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, PR China.
| | - Leihong Xiang
- Department of Dermatology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, PR China.
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32
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Vallerand IA, Lewinson RT, Parsons LM, Hardin J, Haber RM, Lowerison MW, Barnabe C, Patten SB. Vitiligo and major depressive disorder: A bidirectional population-based cohort study. J Am Acad Dermatol 2018; 80:1371-1379. [PMID: 30528503 DOI: 10.1016/j.jaad.2018.11.047] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2018] [Revised: 10/19/2018] [Accepted: 11/21/2018] [Indexed: 12/30/2022]
Abstract
BACKGROUND Vitiligo patients often report their mental health has an effect on their skin. However, it is unknown as to whether a common mental disorder, such as major depressive disorder (MDD), can also precipitate the onset of vitiligo. OBJECTIVE Evaluate a bidirectional relationship between MDD and vitiligo using The Health Improvement Network database. METHODS Incident MDD and referent cohorts were followed until the development of vitiligo. Also, incident vitiligo and referent cohorts were followed until the development of MDD. Cox proportional hazards models were used, and numerous covariates were adjusted for. RESULTS In adjusted models, MDD patients (n = 405,397) were at a 64% increased risk for vitiligo (hazard ratio 1.64, 95% confidence interval [CI] 1.43-1.87, P < .0001) compared with the referent cohort (n = 5,739,048). This risk was decreased in patients using antidepressants. Compared with the referent cohort (n = 6,137,696), patients with vitiligo (n = 7104) that were <30 years of age at diagnosis had a higher risk of developing MDD than patients ≥30 years of age (hazard ratio 1.31, 95% CI 1.14-1.50, P < .0001 vs 1.22, 95% CI 1.08-1.37, P = .001, respectively). LIMITATIONS This study did not evaluate the severity of MDD or vitiligo on outcome development. CONCLUSION These results highlight the burden of depression in patients with vitiligo and support the possible existence of pathophysiological connections between these 2 conditions.
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Affiliation(s)
- Isabelle A Vallerand
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Canada.
| | - Ryan T Lewinson
- Division of Dermatology, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Laurie M Parsons
- Division of Dermatology, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Jori Hardin
- Division of Dermatology, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Richard M Haber
- Division of Dermatology, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Mark W Lowerison
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Canada; Clinical Research Unit, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Cheryl Barnabe
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Canada; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Scott B Patten
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Canada; Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Canada
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33
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Gomes IA, de Carvalho FO, de Menezes AF, Almeida FM, Shanmugam S, de Souza Siqueira Quintans J, Quintans-Júnior LJ, de Moura TR, Oliveira PD, de Souza Araújo AA. The role of interleukins in vitiligo: a systematic review. J Eur Acad Dermatol Venereol 2018; 32:2097-2111. [PMID: 29704266 DOI: 10.1111/jdv.15016] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 03/20/2018] [Indexed: 12/30/2022]
Abstract
Vitiligo is a disorder of the skin that causes depigmentation and asymptomatic macules whose exact cause is still unclear. Although its aetiology is not fully elucidated, the main theory of its pathomechanism is that it is associated with the autoimmune process. There is few summarized information about the role of inflammatory mediators, as interleukins, in vitiligo, so our aim was to present a systematic review of the role of interleukins in vitiligo, focusing on interleukins. In this review, we included all studies assessing interleukin levels in vitiligo patients conducted up to June 2017. Quality assessment of these studies was performed using the Newcastle-Ottawa Scale (NOS). The interleukins mainly involved were IL-2, IL-4, IL-6, IL-10 and IL-17. The studies highlight the crucial role of IL-17 in the onset and progression of the disease, and its synergistic action with IL-2, IL-6 and IL-33. Dysregulated levels of the interleukins were also correlated with the stage of disease, the affected skin surface area, and indicated as the main factor for lymphocyte infiltration found in depigmented regions. These findings illustrate the growing need for new therapies targeting vitiligo and further research into the role of interleukins as an area of particular interest.
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Affiliation(s)
- I A Gomes
- Programa de Pós-Graduação em Ciências Farmacêuticas da Universidade Federal de Sergipe - UFS, Campus Universitário "Prof. Aloísio de Campos", São Cristóvão, SE, Brazil
| | - F O de Carvalho
- Núcleo de Pós-Graduação em Medicina da Universidade Federal de Sergipe - UFS, Rua Cláudio Batista S/N Bairro Sanatório, Aracaju, SE, Brasil
| | - A F de Menezes
- Núcleo de Pós-Graduação em Medicina da Universidade Federal de Sergipe - UFS, Rua Cláudio Batista S/N Bairro Sanatório, Aracaju, SE, Brasil
| | - F M Almeida
- Departamento de Farmácia, Universidade Federal de Sergipe, Campus Universitário "Prof. Aloísio de Campos", São Cristóvão, SE, Brazil
| | - S Shanmugam
- Programa de Pós-Graduação em Ciências Farmacêuticas da Universidade Federal de Sergipe - UFS, Campus Universitário "Prof. Aloísio de Campos", São Cristóvão, SE, Brazil
| | - J de Souza Siqueira Quintans
- Departamento de Fisiologia, Universidade Federal de Sergipe, Campus Universitário "Prof. Aloísio de Campos", São Cristóvão, SE, Brazil
| | - L J Quintans-Júnior
- Departamento de Fisiologia, Universidade Federal de Sergipe, Campus Universitário "Prof. Aloísio de Campos", São Cristóvão, SE, Brazil
| | - T R de Moura
- Departamento de Fisiologia, Universidade Federal de Sergipe, Campus Universitário "Prof. Aloísio de Campos", São Cristóvão, SE, Brazil
| | - P D Oliveira
- Programa de Pós-Graduação em Ciências Farmacêuticas da Universidade Federal de Sergipe - UFS, Campus Universitário "Prof. Aloísio de Campos", São Cristóvão, SE, Brazil
| | - A A de Souza Araújo
- Programa de Pós-Graduação em Ciências Farmacêuticas da Universidade Federal de Sergipe - UFS, Campus Universitário "Prof. Aloísio de Campos", São Cristóvão, SE, Brazil
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Ochoa-Ramírez LA, Becerra-Loaiza DS, Díaz-Camacho SP, Muñoz-Estrada VF, Ríos-Burgueño ER, Prado-Montes de Oca E, Rangel-Villalobos H, Velarde-Félix JS. Association of human beta-defensin 1 gene polymorphisms with nonsegmental vitiligo. Clin Exp Dermatol 2018; 44:277-282. [DOI: 10.1111/ced.13697] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/22/2018] [Indexed: 12/14/2022]
Affiliation(s)
- L. A. Ochoa-Ramírez
- Faculty of Chemical and Biological Sciences; Autonomous University of Sinaloa; Culiacan Sinaloa Mexico
| | - D. S. Becerra-Loaiza
- Faculty of Chemical and Biological Sciences; Autonomous University of Sinaloa; Culiacan Sinaloa Mexico
| | - S. P. Díaz-Camacho
- Faculty of Chemical and Biological Sciences; Autonomous University of Sinaloa; Culiacan Sinaloa Mexico
| | - V. F. Muñoz-Estrada
- Center of Research and Teaching in Health Sciences (CIDOCS); Autonomous University of Sinaloa; Culiacan Sinaloa Mexico
| | - E. R. Ríos-Burgueño
- Center of Research and Teaching in Health Sciences (CIDOCS); Autonomous University of Sinaloa; Culiacan Sinaloa Mexico
| | - E. Prado-Montes de Oca
- Personalized Medicine National Laboratory (LAMPER); Medical and Pharmaceutical Biotechnology; Research Center in Technology and Design Assistance of Jalisco State (CIATEJ); National Council of Science and Technology (CONACYT); Jalisco Mexico
| | - H. Rangel-Villalobos
- Molecular Genetics Research Institute; University of Guadalajara (CUCI-UdeG); Ocotlan Jalisco Mexico
| | - J. S. Velarde-Félix
- Faculty of Chemical and Biological Sciences; Autonomous University of Sinaloa; Culiacan Sinaloa Mexico
- Faculty of Biology; Autonomous University of Sinaloa; Culiacan Sinaloa Mexico
- General Hospital of Culiacan; Servicios de Salud Sinaloa; Culiacan Mexico
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Wang LM, Zhang B, Li JJ, Zhou YC, Wang DX. The expression change of RORγt, BATF, and IL-17 in Chinese vitiligo patients with 308 nanometers excimer laser treatment. Dermatol Ther 2018; 31:e12598. [PMID: 29642271 DOI: 10.1111/dth.12598] [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: 11/06/2017] [Revised: 12/21/2017] [Accepted: 03/18/2018] [Indexed: 11/29/2022]
Abstract
This study aims to explore the expression of RORγt, BATF, and IL-17 in Chinese vitiligo patients with 308 nm excimer laser treatment. One hundred and sixty-four vitiligo patients treated with 308 nm excimer laser were enrolled as Case group and 137 health examiners as Control group. Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to detect the expressions of RORγt, BATF, and IL-17. Expression of RORγt, BATF, IL-17A, and IL-17F were higher in Case group than Control group, with the diagnostic accuracy of 88.04, 87.38, 97.34, and 89.04%, respectively. Pearson correlation analysis showed a positive correlation in RORγt, BATF, IL-17A, and IL-17F mRNAs in vitiligo patients. Moreover, their expressions were higher in active vitiligo patients than stable ones. Besides, the expressions of RORγt, BATF, IL-17A, and IL-17F in vitiligo skin were significantly higher than those in non lesional skin and normal controls. After treatment, their expressions were significantly decreased. Active vitiligo and the high expressions of RORγt, BATF, and IL-17F were the independent risk factors for the ineffectiveness of 308 nm excimer laser treatment. The expressions of RORγt, BATF, IL-17 were significantly enhanced in vitiligo patients, which were correlated with the activity of vitiligo and 308 nm excimer laser therapeutic effects.
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Affiliation(s)
- Lu-Mei Wang
- Department of Dermatology, Dong Guan People's Hospital, Guangdong Province, Dongguan 523018, People's Republic of China
| | - Bin Zhang
- Department of Gynaecology and Obstetrics, Dong Guan People's Hospital, Guangdong Province, Dongguan 523018, People's Republic of China
| | - Jun-Jie Li
- Department of Dermatology, Dong Guan People's Hospital, Guangdong Province, Dongguan 523018, People's Republic of China
| | - Yun-Cong Zhou
- Department of Dermatology, Dong Guan People's Hospital, Guangdong Province, Dongguan 523018, People's Republic of China
| | - Dong-Xia Wang
- Department of Interventional Therapy, Dong Guan People's Hospital, Guangdong Province, Dongguan 523018, People's Republic of China
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Pregnancy outcomes in patients with vitiligo: A nationwide population-based cohort study from Korea. J Am Acad Dermatol 2018; 79:836-842. [PMID: 29477741 DOI: 10.1016/j.jaad.2018.02.036] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 01/31/2018] [Accepted: 02/10/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Vitiligo is a chronic autoimmune skin disorder affecting 1% of populations worldwide. Few large-scale studies have explored adverse pregnancy outcomes in patients with vitiligo. OBJECTIVE To investigate adverse pregnancy outcomes in patients with vitiligo. METHODS We performed a retrospective cohort study on 4738 pregnancies of women with vitiligo and 47,380 pregnancies of age-matched controls without vitiligo using the Korean National Health Insurance Claims database from 2007 to 2016. Multivariate logistic regression models were used to evaluate the associations between vitiligo and pregnancy outcomes, including live births, spontaneous abortion, cesarean delivery, preterm delivery, gestational diabetes mellitus, stillbirth, pre-eclampsia/eclampsia, and intrauterine growth retardation. RESULTS Patients with vitiligo exhibited a significantly lower live birth rate (odds ratio, 0.870; 95% confidence interval, 0.816-0.927) and a higher incidence of spontaneous abortion (odds ratio, 1.250; 95% confidence interval, 1.148-1.362) than the control group. LIMITATION The Korean National Health Insurance Claims database lacks detailed clinical information on individual patients. CONCLUSION Vitiligo was significantly associated with an increased risk of spontaneous abortion. Further studies are needed to determine whether systemic autoimmunity explains our finding.
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Psycho-Neuro-Endocrine-Immunology: A Psychobiological Concept. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 996:123-134. [PMID: 29124696 DOI: 10.1007/978-3-319-56017-5_11] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Psycho-Neuro-Endocrine-Immunology (P.N.E.I.) is a scientific field of study that investigates the link between bidirectional communications among the nervous system, the endocrine system, and the immune system and the correlations of this cross-talk with physical health. The P.N.E.I. innovative medical approach represents a paradigm shift from a strictly biomedical view of health and disease taken as hermetically sealed compartments to a more interdisciplinary one. The key element of P.N.E.I. approach is represented by the concept of bidirectional cross-talk between the psychoneuroendocrine and immune systems. The Low Dose Medicine is one of the most promising approaches able to allow the researchers to design innovative therapeutic strategies for the treatment of skin diseases based on the rebalance of the immune response.
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