• T cells
• autoimmune liver disease
• myeloid‐derived suppressor cells
• treatment
• viral hepatitis

• 2022ZDLSF03-03 Key Research and Development Program of Shaanxi
• 82270551 National Natural Science Foundation of China

• TIGIT+Vδ2 t cells
• Tfh1 cells
• autoimmune hepatitis
• primary biliary cholangitis
• γδ T cells

• Humans
• Hepatitis, Autoimmune/immunology
• Hepatitis, Autoimmune/diagnosis
• Hepatitis, Autoimmune/pathology
• Liver Cirrhosis, Biliary/immunology
• Liver Cirrhosis, Biliary/diagnosis
• Male
• Female
• Middle Aged
• T-Lymphocyte Subsets/immunology
• Adult
• Aged
• CD8-Positive T-Lymphocytes/immunology
• Cytokines/metabolism

• 82070574 National Natural Science Foundation of China
• 2020A1515111203 Applied Basic Research Fund of Guangdong Province
• 2016A030313112 Natural Science Foundation of Guangdong Province
• 2021A1515010420 Guangdong Basic and Applied Basic Research Foundation

• Esophageal squamous cell carcinoma
• Interleukin 33
• Tumor microenvironment
• Tumor necrosis factor-alpha
• Unsupervised clustering analysis

• Humans
• Prognosis
• Cytokines/blood
• Esophageal Squamous Cell Carcinoma/blood
• Esophageal Squamous Cell Carcinoma/pathology
• Esophageal Squamous Cell Carcinoma/mortality
• Biomarkers, Tumor/blood
• Male
• Female
• Esophageal Neoplasms/blood
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/mortality
• Cluster Analysis
• Middle Aged
• Aged

• C4
• gammaglobulins
• monocyte to lymphocyte ratio
• neutrophil to lymphocyte ratio
• peripheral neuropathy
• primary Sjögren syndrome
• vitamin D

• PN-III-P2-2.1-PED-2021-2243 Unitatea Executiva Pentru Finantarea Invatamantului Superior a Cercetarii Dezvoltarii si Inovarii

• eye diseases
• haematological diseases

• Humans
• Hepatitis, Autoimmune/diagnosis
• Hepatitis, Autoimmune/drug therapy
• Quality of Life
• Azathioprine/therapeutic use
• Biomarkers
• Liver Cirrhosis/drug therapy
• Immunosuppressive Agents/therapeutic use

• UL1 TR001863 NCATS NIH HHS

• Autoimmune hepatitis
• Biologic agents
• Refractory
• Therapy

• IFN-γ
• IL-10
• IL-6
• Infectious mononucleosis in children
• TNF-α
• Th1/Th2 immunocytokines
• VCA-IgM

Obesity is a chronic process and could activate various inflammatory responses, which in turn aggravates obesity and related metabolic syndrome. Here we explored whether long-term inhibition of inflammation could successfully alleviate high-fat diet (HFD)-induced obesity.

We constructed stable overexpressing interleukin 10 (IL10) human umbilical cord-derived mesenchymal stromal cells (HUCMSCs) which repeatedly were applied to obesity mice with HFD feeding to obtain a long-term anti-inflammation based on the prominent anti-inflammation effects of IL10 and immunomodulatery effects of HUCMSCs. Then we monitored the features of obesity including body weight, serum ALT, AST, and lipids. In addition, glucose homeostasis was determined by glucose tolerance and insulin sensitivity tests. The infiltrated macrophages in adipose tissues and hepatic lipid accumulation were detected, and the expressions of adipogenesis and inflammatory genes in adipose tissues were examined by real-time (RT) PCR and western blot analysis.

Compared with HUCMSCs, IL10-HUCMSCs treatment had much better anti-obesity effects including body weight reduction, less hepatic lipids accumulation, lower amount and size of adipocyte, greater glucose tolerance, less systemic insulin resistance, and less adipose tissue inflammation in HFD feeding mice. Finally, IL10-HUCMSCs could decrease the activation of MAPK JNK of adipose tissue induced by HFD. The inhibition of MAPK JNK signal pathway by a small chemical molecule SP600125 in 3T3-L1 cells, a preadipocyte line, reduced the differentiation of adipocytes and lipid droplet accumulation.

A lasting anti-inflammation based on gene modified stem cell therapy is an effective strategy in preventing diet-induced obesity and obesity-related metabolic syndrome.

• Adipose tissue
• Anti-inflammation
• Gene modification
• IL10
• MAPK
• Obesity
• Stem cell therapy
• mesenchymal stromal cells (MSCs)

• Autoimmune hepatitis
• Hepatic inflammation
• Indicator
• Liver fibrosis
• Serum CD48

Autoimmune hepatitis (AIH) is a chronic progressive liver disease whose etiology and pathogenesis are not yet clear. It is currently believed that the occurrence of AIH is closely related to genetic susceptibility and immune abnormalities, and other factors such as environment, viral infection and drugs that may cause immune dysfunction. This article reviews the pathogenesis of AIH and describes the latest research results in the past 5 years.

• Autoimmune hepatitis
• Genetic susceptibility
• environmental factors
• Immunomodulation
• Drug-induced liver injury
• Intestinal microbes

• CD4+
• Concanavalin A
• Etanercept
• IL-4
• Liver injury
• TNF-α

• Animals
• Anti-Inflammatory Agents/pharmacology
• CD4-Positive T-Lymphocytes/immunology
• Chemical and Drug Induced Liver Injury/drug therapy
• Chemical and Drug Induced Liver Injury/etiology
• Chemical and Drug Induced Liver Injury/pathology
• Concanavalin A/toxicity
• Cytokines/metabolism
• Etanercept/pharmacology
• Hepatitis/drug therapy
• Hepatitis/etiology
• Hepatitis/pathology
• Immunosuppressive Agents/pharmacology
• Male
• Mice
• Mice, Inbred BALB C
• Mitogens/toxicity
• Signal Transduction

• IL-33
• ST2
• autoimmune disorders
• pathogenic
• protective

25-Hydroxyvitamin D [25(OH)D] has been reported to be associated with several chronic liver diseases. The relationship between 25(OH)D and autoimmune hepatitis (AIH) pathogenesis is incompletely understood. We investigated the association of serum total and free 25(OH)D levels with necroinflammatory activity and cytokine levels in 66 patients with AIH diagnosed in our hospital. The median age at AIH diagnosis was 57 years, and the male:female ratio was 7:59. The median serum total 25(OH)D level in therapy-naïve patients with AIH was 14.2 ng/mL (interquartile range [IQR], 11.4–17.9 ng/mL). Of the 66 patients with AIH, 36 had serum total 25(OH)D levels of < 15 ng/mL and were considered to have vitamin D deficiency, and 30 had serum total 25(OH)D levels of ≥ 15 ng/mL. Patients with acute-onset AIH had significantly lower serum total 25(OH)D levels than those with chronic-onset AIH. In particular, serum total 25(OH)D levels were significantly lower in patients with severe forms of AIH. Furthermore, the serum total 25(OH)D level was positively correlated with the serum albumin level and prothrombin time and negatively correlated with the serum total bilirubin level and necroinflammatory activity in AIH. Multivariate logistic regression analysis showed that the serum total 25(OH)D level was an independent factor for severe necroinflammatory activity. Interestingly, AIH patients with serum total 25(OH)D levels of < 15 ng/mL had higher levels of inflammatory cytokines such as interferon-γ and interleukin-33. Free 25(OH)D levels were correlated with total 25(OH)D levels, and the percentage of free 25(OH)D was significantly associated with necroinflammatory activity. In conclusion, 25(OH)D deficiency may play an important role in predicting AIH severity via inflammatory cytokine production.

Follicular helper T (TFH) cell provides germinal centre (GC) B cell with critical signals for autoantibody production in the immunopathogenesis and progression of autoimmune hepatitis (AIH). However, the immunoregulatory functions of follicular regulatory T (TFR) cell in AIH are still unclear. The numbers of circulating TFR/TFH cells were measured in AIH patients. Moreover, we established experimental autoimmune hepatitis (EAH) model to examine the function of TFR cells on B‐cell differentiation and autoantibody production in vivo and vitro. AIH patients had significantly increased numbers of TFH cells and decreased numbers of TFR cells as well as imbalanced TFR/TFH‐type cytokines (IL‐10, TGF‐β1 and IL‐21) compared with healthy controls (HCs). In addition, TFR cell numbers negatively correlated with TFH cell numbers. Also, serum hypergammaglobulinaemia (IgG and IgM) concentration negatively correlated the levels of serum IL‐21, but positively correlated with the levels of serum IL‐10 in AIH patients. Furthermore, in comparison with control group, significantly higher frequencies of spleen TFR cells but lower frequencies of spleen TFH cells were detected in the EAH group. Further analysis found that TFR cells simultaneously express the phenotypic characteristics of Treg and TFH cells, but exercise as negative regulators of autoantibody production in vitro culture. Our findings demonstrated that dysregulated between TFR and TFH cells might cause excessive production of autoantibodies and destruction of the immune homeostasis, leading to the immunopathological process in AIH.

• AIH
• EAH
• TFH cells
• TFR cells

• IL-10
• IL-4
• NF-κb
• Retinoic acid
• T-cells

Interleukin (IL)‐33 was recently described as a new member of the IL‐1 family; members of this family have proinflammatory activity. IL‐33 and its soluble receptor ST2 (sST2) have been implicated in the pathogenesis of autoimmune diseases. This study investigated serum IL‐33 and sST2 in type I autoimmune hepatitis (AIH) and the relationship of these molecules with clinical and pathologic parameters. Subjects included 65 patients with AIH who were diagnosed in our hospital. The control population included 17 healthy individuals and 36 patients with primary biliary cholangitis (PBC). Mean age at AIH diagnosis was 55.5 years, and the male‐to‐female ratio was 6:59. Serum IL‐33 and sST2 levels were significantly higher in patients with AIH than in those with PBC or controls. Importantly, immunohistochemistry revealed high IL‐33 expression in liver sections from patients with AIH. In particular, serum IL‐33 and sST2 levels were significantly higher in acute‐onset AIH than in chronic‐onset AIH. Serum IL‐33 levels were positively correlated with serum total bilirubin (TB), alanine aminotransferase (ALT), and necroinflammatory activity in AIH. We performed multivariate logistic regression analysis and found serum IL‐33 levels to be independent factors for severe activity. Serum sST2 levels were positively correlated with serum TB and ALT and negatively correlated with serum albumin and prothrombin time in AIH. In particular, serum sST2 levels were significantly higher in severe symptoms of AIH. Serum IL‐33 and sST2 levels in patients with AIH responsive to treatment with prednisolone were significantly decreased after treatment. Interestingly, serum IL‐33 level was associated with a significantly increased risk of relapse. Conclusion: IL‐33/ST2 may play an important role in the pathogenesis and severity of AIH and may be a promising target for AIH therapy.

This study aimed to investigate serum IL‐33 and sST2 in type I autoimmune hepatitis (AIH) patients and its relationship with clinical and pathological parameters. Multivariate analysis was performed, and serum IL‐33 levels were independent factors for severe activity and relapse. Our findings suggest that IL‐33/ST2 may play an important role in the pathogenesis and severity of AIH and may present a promising target for AIH therapy.

The development of colorectal cancer (CRC) is not only determined by transformed cells per se, but also by factors existing in their immune microenvironment. Accumulating scientific evidence has revealed that interleukin (IL)-33, an IL-1 family member, plays an essential role in the regulation of immune response and is relevant in CRC pathogenesis. Data from both human and experimental studies demonstrated that IL-33 inhibits host anti-tumor immunity, remodels tumor stroma and enhances angiogenesis, thereby promoting the development of CRC. These pro-tumor effects of IL-33 are mainly mediated by IL-33 receptor ST2 (also known as IL-1RL1). Based on those findings, it is currently hypothesized that the IL-33/ST2 pathway is a potential biomarker and therapeutic target for colorectal tumorigenesis. Herein, we summarize the recent discoveries in understanding the critical role of the IL-33/ST2 pathway in contributing to the pathogenesis of colorectal tumorigenesis and discuss its potential implications for the future development of effective anti-tumor strategies.

• IL-33
• ST2
• colorectum
• cytokine
• tumorigenesis

Interleukin-33 (IL-33), considered as an alarmin released upon tissue stress or damage, is a member of the IL-1 family and binds the ST2 receptor. First described as a potent initiator of type 2 immune responses through the activation of T helper 2 (T_H2) cells and mast cells, IL-33 is now also known as an effective stimulator of T_H1 immune cells, natural killer (NK) cells, iNKT cells, and CD8 T lymphocytes. Moreover, IL-33 was shown to play an important role in several cancers due to its pro and anti-tumorigenic functions. Currently, IL-33 is a possible inducer and prognostic marker of cancer development with a direct effect on tumor cells promoting tumorigenesis, proliferation, survival, and metastasis. IL-33 also promotes tumor growth and metastasis by remodeling the tumor microenvironment (TME) and inducing angiogenesis. IL-33 favors tumor progression through the immune system by inducing M2 macrophage polarization and tumor infiltration, and upon activation of immunosuppressive cells such as myeloid-derived suppressor cells (MDSC) or regulatory T cells. The anti-tumor functions of IL-33 also depend on infiltrated immune cells displaying T_H1 responses. This review therefore summarizes the dual role of this cytokine in cancer and suggests that new proposals for IL-33-based cancer immunotherapies should be considered with caution.

• cancer
• immunity
• immunosuppression
• interleukin-33
• microenvironment

In sterile liver inflammation, danger signals are released in response to tissue injury to alert the immune system; e.g., by activation of the NLRP3 inflammasome. Recently, IL-33 has been identified as a novel type of danger signal or “alarmin”, which is released from damaged and necrotic cells. IL-33 is a pleiotropic cytokine that targets a broad range of immune cells and exhibits pro- and anti-inflammatory properties dependent on the disease. This review summarizes the immunomodulatory roles of the NLRP3 inflammasome and IL-33 in sterile liver inflammation and highlights potential therapeutic strategies targeting these pathways in liver disease.

• IL-1β
• IL-33
• ILC2
• NLRP3 inflammasome
• sterile liver inflammation
• tregs