The immunobiology of mucosal-associated invariant T cell (MAIT) function in primary biliary cholangitis: Regulation by cholic acid-induced Interleukin-7

Jiang, Xiang; Lian, Min; Li, Yanmei; Zhang, Weici; Wang, Qixia; Wei, Yiran; Zhang, Jun; Chen, Weihua; Xiao, Xiao; Miao, Qi; Bian, Zhaolian; Qiu, Dekai; Fang, Jing‐Yuan; Ansari, Aftab A.; Leung, Patrick S.C.; Coppel, Ross L.; Tang, Ruqi; Gershwin, M. Eric; Ma, Xiong

doi:10.1016/j.jaut.2018.01.007

Cited by 52 publications

(78 citation statements)

References 60 publications

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“…This finding is consistent with previous studies that reported reduced abundance of MAIT cells in peripheral blood 10,25 and in liver tissues 10 of PBC patients compared to healthy controls. Setsu et al observed that depleted MAIT cells were not recovered to normal levels in the blood of PBC patients even after UDCA treatment, suggesting the possibility that MAIT cells were being activated, exhausted, and depleted due to ongoing liver inflammation 10 .…”

Section: Discussionsupporting

confidence: 93%

Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

Jang

Juran

Cunningham

et al. 2020

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The relationship between Primary Biliary Cholangitis (PBC), a chronic cholestatic autoimmune liver disease, and the peripheral immune system remains to be fully understood. Herein, we performed the first mass cytometry (CyTOF)-based, immunophenotyping analysis of the peripheral immune system in PBC at single-cell resolution. CyTOF was performed on peripheral blood mononuclear cells (PBMCs) from PBC patients (n=33) and age-/sex-matched healthy controls (n=33) to obtain immune cell abundance and marker expression profiles. Hiearchical clustering methods were applied to identify immune cell types and subsets significantly associated with PBC. Subsets of gamma-delta T cells (CD3 + TCRgd + ), CD8 + T cells (CD3 + CD8 + CD161 + PD1 + ), and memory B cells (CD3 -CD19 + CD20 + CD24 + CD27 + ) were found to have lower abundance in PBC than in control. In contrast, higher abundance of subsets of monocytes and naïve B cells were observed in PBC compared to control. Furthermore, several naïve B cell (CD3 -CD19 + CD20 + CD24 -CD27 -) subsets were significantly higher in PBC patients with cirrhosis (indicative of late-stage disease) than in those without cirrhosis. Alternatively, subsets of CD8 + CD161 + T cells and memory B cells were lower in abundance in cirrhotic relative to non-cirrhotic PBC patients.Future immunophenotyping investigations could lead to better understanding of PBC pathogenesis and progression, and also to the discovery of novel biomarkers and treatment strategies.

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Section: Discussionsupporting

confidence: 93%

Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

Jang

Juran

Cunningham

et al. 2020

Preprint

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“…Our study shows that the frequency of peripheral MAIT cells in patients with CVH was significantly reduced compared to healthy controls. In line with our findings, previous studies have also shown the level of peripheral MAIT cells were significantly lower in infectious diseases such as HIV infection (35) and primary biliary cholangitis (10). MAIT cells have been reported to home to peripheral tissues, especially the intestine and the liver with high expression of chemokine receptors CCR5, CCR6, and CXCR6 (36).…”

Section: Discussionsupporting

confidence: 91%

“…Koay et al reported PLZF as a controlling transcription factor for three developmental stages of maturation and function of MAIT cells (9). Most studies have defined MAIT cells as CD3 + CD161 high Vα7.2+ lymphocytes (10)(11)(12)(13). MAIT cells recognize Vitamin B2 (riboflavin) metabolites produced by bacteria and yeasts in a major histocompatibility complexrelated protein 1 (MR1)-dependent manner (14,15) and can be activated in an MR1-independent fashion in response to cytokines (7,(16)(17)(18).…”

Section: Contextmentioning

confidence: 99%

Immune Profile of Mucosal-Associated Invariant T Cells in Chronic Viral Hepatitis: A Systematic Review and Meta-Analysis

et al. 2019

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Context: Chronic viral hepatitis (CVH), a world health problem, is the leading cause of hepatocellular carcinoma (HCC). Host immunity plays a critical role in viral clearance, development and progression of the disease. Mucosal-associated invariant T (MAIT) cells represent an abundant form of innate T cells, which plays an essential role in infectious diseases with releasing cytokine, lysing target cells, and shaping adaptive immunity. Objectives: Although numerous studies showed the immune profiles of MAIT cells in CVH, the results are inconsistent. Thus, we performed a meta-analysis to analyze the immune profiles of MAIT cells in CVH. Evidence Acquisition: PubMed, Embase, the Cochrane Library, Google Scholar, ScienceDirect, Web of Science, and the China National Knowledge Infrastructure (CNKI) were searched and 10 studies were included. Data from each study were compared using the standardized mean difference (SMD) with 95% confidence interval (CI). The quality assessment of studies and publication bias were evaluated by Newcastle-Ottawa scale and Begg's and Egger's tests, respectively, and a P value of < 0.05 was considered statistically significant. Results: Meta-analysis of the enrolled studies showed that the frequency of MAIT cells was significantly lower in patients with CVH as compared to healthy controls (SMD =-0.90, 95%

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“…Cholic acid-induced IL-7 production in hepatocytes plays a critical role in regulating MAIT cell function, highlighting that hepatocytes may bridge cholangiocyte injury and innate immunity through a bile acid signaling pathway. 171…”

Section: Innate Immunitymentioning

confidence: 99%

The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review

et al. 2019

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Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune destruction of small to medium size intrahepatic bile ducts. The etiology of PBC remains unknown and pathogenesis features immune-mediated biliary injury, alongside the consequences of chronic cholestasis. PBC is strongly associated with the loss of immune tolerance against mitochondrial antigens and the subsequent presence of an articulated immunologic response that involves both humoral and cellular responses. Both environmental factors and genetic variants increase PBC susceptibility. Biliary epithelial cells have often been considered a passive target of the immune attack in PBC; however, cholangiocyte dedifferentiation, senescence, stress, and deoxyribonucleic acid damage have been recognized to play an active role in the pathogenesis of PBC. This review highlights and discusses the most relevant pathogenetic mechanisms in PBC, focusing on the key factors that lead to the onset of cholestasis and immune activation.

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The immunobiology of mucosal-associated invariant T cell (MAIT) function in primary biliary cholangitis: Regulation by cholic acid-induced Interleukin-7

Cited by 52 publications

References 60 publications

Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

Immune Profile of Mucosal-Associated Invariant T Cells in Chronic Viral Hepatitis: A Systematic Review and Meta-Analysis

The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review

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