Incorporating mucosal-associated invariant T cells into the pathogenesis of chronic liver disease

Czaja, Albert J.

doi:10.3748/wjg.v27.i25.3705

Cited by 11 publications

(8 citation statements)

References 221 publications

(550 reference statements)

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“…We will focus on what is known about the contribution of MAIT cells to inflammatory processes in the liver and will provide a limited description of data on blood MAIT cells in the discussed patient populations. A very thorough review of the contribution of both peripheral and liver MAIT cells to the pathogenesis of chronic liver disease was recently published [ 67 ].…”

Section: Mait Cells In the Inflamed Livermentioning

confidence: 99%

MAIT cells in liver inflammation and fibrosis

et al. 2022

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Mucosal-associated invariant T cells or MAIT cells are an abundant cell type in humans and especially so in the liver. MAIT cells are a subset of T lymphocytes that sit at a bridge between innate and adaptive immunity, so-called innate-like or “unconventional” T cells. The specificity of their antigen receptor (T cell receptor or TCR) is for the conserved major histocompatibility complex (MHC)-related molecule MR1, which presents a modified bacterial metabolite from the vitamin B2 biosynthesis pathway – this allows them to respond in the presence of many bacteria or yeast. MAIT cells also possess an array of cytokine receptors, which allows triggering independently of the TCR. The combination of such signals drives their functionality – this means they can respond to a range of stimuli and likely play a role not only in infection or inflammation, but also under homeostatic conditions.In this review, we will look at the question of what MAIT cells are doing in the normal liver and how they behave in the setting of disease. These questions are of relevance because MAIT cells are such a distinctive cell type enriched in the liver under normal conditions, and their modulation could be of therapeutic benefit. The recent discovery that they appear to be involved in liver fibrosis is particularly of interest in this context.

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Section: Mait Cells In the Inflamed Livermentioning

confidence: 99%

MAIT cells in liver inflammation and fibrosis

et al. 2022

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“…Recent reports show the existence of a tissue repair gene signature in liver-derived MAIT cells, which can be induced by TCR activation [ 24 ]. More studies examining the function of MAIT cells in patients with NAFLD in response to diet and exercise alone and in combination are needed to better understand the role of MAIT cells in disease pathogenesis in patients with NASH and other chronic liver diseases [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Dietary versus Exercise Intervention on Intrahepatic MAIT Cells and Histological Features of NAFLD

Naimimohasses

O’Gorman

Wright³

et al. 2022

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Background: Mucosal-associated invariant T (MAIT) cells promote inflammation in obesity and are implicated in the progression of non-alcoholic fatty liver disease (NAFLD). However, as the intrahepatic MAIT cell response to lifestyle intervention in NAFLD has not been investigated, this work aimed to examine circulating and intrahepatic MAIT cell populations in patients with NAFLD, after either 12 weeks of dietary intervention (DI) or aerobic exercise intervention (EI). Methods: Multicolour flow cytometry was used to immunophenotype circulating and intrahepatic MAIT cells and measure MAIT cell expression (median fluorescence intensity, MFI) of the activation marker CD69 and apoptotic marker CD95. Liver histology, clinical parameters, and MAIT cell populations were assessed at baseline (T0) and following completion (T1) of DI or EI. Results: Forty-five patients completed the study. DI participants showed decreased median (interquartile range) expression of the activation marker CD69 on circulating MAIT cells (T0: 104 (134) versus T1 27 (114) MFI; p = 0.0353) and improvements in histological steatosis grade post-intervention. EI participants showed increased expression of the apoptotic marker CD95, both in circulating (T0: 1549 (888) versus T1: 2563 (1371) MFI; p = 0.0043) and intrahepatic MAIT cells (T0: 2724 (862) versus T1: 3117 (1622) MFI; p = 0.0269). Moreover, the percentage of intrahepatic MAIT cells significantly decreased after EI (T0: 11.1 (14.4) versus T1: 5.3 (9.3)%; p = 0.0029), in conjunction with significant improvements in fibrosis stage and hepatocyte ballooning. Conclusions: These data demonstrate independent benefits from dietary and exercise intervention and suggest a role for intrahepatic MAIT cells in the observed histological improvements in NAFLD.

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“…In this study, CTLA-4 positivity was also higher in MAIT cells. Combined, it was proposed that MAIT cells were exhausted in AIH ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Standard immunosuppressive treatment reduces regulatory B cells in children with autoimmune liver disease

et al. 2023

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IntroductionAutoimmune hepatitis (AIH) is a chronic liver disease caused by a perturbed immune system. The scarcity of short- and long-term immune monitoring of AIH hampered us to comprehend the interaction between immunosuppressive medication and immune homeostasis.Methods and patientsWe recruited children with AIH at the time of diagnosis and at the 1st, 3rd, 6th, 12th, 18th, and 24th months of immunosuppression (IS). We also enrolled children with AIH being on IS for >2 years. Children with drug-induced liver injury (DILI), and those receiving tacrolimus after liver transplantation (LT), were enrolled as disease/IS control subjects. Healthy children (HC) were also recruited. Peripheral blood mononuclear cells (PBMCs) were isolated from all participants. Healthy liver tissue from adult donors and from livers without inflammation were obtained from children with hepatoblastoma. By using flow cytometry, we performed multi-parametric immune profiling of PBMCs and intrahepatic lymphocytes. Additionally, after IS with prednisolone, tacrolimus, rapamycin, or 6-mercaptopurine, we carried out an in vitro cytokine stimulation assay. Finally, a Lifecodes SSO typing kit was used to type HLA-DRB1 and Luminex was used to analyze the results.ResultsUntreated AIH patients had lower total CD8 T-cell frequencies than HC, but these cells were more naïve. While the percentage of naïve regulatory T cells (Tregs) (CD4+FOXP3lowCD45RA+) and regulatory B cells (Bregs, CD20+CD24+CD38+) was similar, AIH patients had fewer activated Tregs (CD4+FOXP3highCD45RA-) compared to HC. Mucosal-associated-invariant-T-cells (MAIT) were also lower in these patients. Following the initiation of IS, the immune profiles demonstrated fluctuations. Bregs frequency decreased substantially at 1 month and did not recover anymore. Additionally, the frequency of intrahepatic Bregs in treated AIH patients was lower, compared to control livers, DILI, and LT patients. Following in vitro IS drugs incubation, only the frequency of IL-10-producing total B-cells increased with tacrolimus and 6MP. Lastly, 70% of AIH patients possessed HLA-DR11, whereas HLA-DR03/DR07/DR13 was present in only some patients.ConclusionHLA-DR11 was prominent in our AIH cohort. Activated Tregs and MAIT cell frequencies were lower before IS. Importantly, we discovered a previously unrecognized and long-lasting Bregs scarcity in AIH patients after IS. Tacrolimus and 6MP increased IL-10+ B-cells in vitro.

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Incorporating mucosal-associated invariant T cells into the pathogenesis of chronic liver disease

Cited by 11 publications

References 221 publications

MAIT cells in liver inflammation and fibrosis

MAIT cells in liver inflammation and fibrosis

Differential Effects of Dietary versus Exercise Intervention on Intrahepatic MAIT Cells and Histological Features of NAFLD

Standard immunosuppressive treatment reduces regulatory B cells in children with autoimmune liver disease

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