Lights on MAIT cells, a new immune player in liver diseases

Toubal, Amine; Lehuen, Agnès

doi:10.1016/j.jhep.2016.02.003

Cited by 14 publications

(13 citation statements)

References 21 publications

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“…MAIT cell frequency is lower in the peripheral blood of patients compared to healthy children. Such decreased frequency could reflect their migration from the blood to inflamed tissues as described in other inflammatory and autoimmune diseases 24–26,29,52–54 and as supported by their increased frequency in the pancreas of NOD mice during T1D development. Lower frequency of blood MAIT cells could also result from their sustained activation leading to cell exhaustion as indicated by their expression of Bcl-2, CD25 and PD1 and by their defective in vitro response.…”

Section: Discussionmentioning

confidence: 64%

Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes

et al. 2017

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Type 1 diabetes is an autoimmune disease resulting from the destruction of pancreatic-beta cells by the immune system involving innate and adaptive immune cells. Mucosal-associated invariant T (MAIT) cells are innate-like T-cells recognizing bacterial riboflavin-precursor derivatives presented by the MHC-I related molecule, MR1. Since T1D is associated with gut microbiota modification, we investigated MAIT cells in this pathology. In T1D patients and non-obese diabetic mice, we detected MAIT cell alterations, including increased granzyme B production, which occur before disease onset. Analysis of NOD mice deficient for MR1 and therefore lacking MAIT cells revealed a loss of gut integrity, increased anti-islet responses associated with exacerbated diabetes. Altogether our data highlight the role of MAIT cells in the maintenance of gut integrity and the control of anti-islet autoimmune responses. MAIT cell monitoring could represent a new biomarker in T1D while their manipulation may open new therapeutic strategies.

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Section: Discussionmentioning

confidence: 64%

Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes

et al. 2017

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“…Human MAIT cells are predominantly of the CD8+ effector memory phenotype. Although double-negative MAIT cells (CD4− CD8−) are present in modest numbers and the CD4+ T lymphocytes make up only a minority of this subset in the peripheral circulation, the relative proportions of MAIT cells alter in chronic liver disease [ 15 , 39 , 41 ]. This diversity leads further credence to their differing roles in the microenvironment depending on their phenotype.…”

Section: Mait Cellsmentioning

confidence: 99%

“…Interestingly, in IBD, MAITs are found to be decreased in number in the blood, but increased at sites of inflammation such as the ileum in Crohns’, thus supporting the concept of cell trafficking. MAITs are, however, also found in the lamina propria of healthy individuals [ 41 , 63 ]. Some investigators observed that MAITs in IBD patients were expressing higher levels of caspase, which indicate their apoptotic nature within this disease [ 12 , 64 ].…”

Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 99%

Linking the gut and liver: crosstalk between regulatory T cells and mucosa-associated invariant T cells

Atif

Warner

2018

Hepatol Int

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The gut–liver axis is increasingly considered to play a vital part in the progression of chronic inflammatory gut and liver diseases. Hence, a detailed understanding of the local and systemic regulatory mechanisms is crucial to develop novel therapeutic approaches. In this review, we discuss in-depth the roles of regulatory T cells (Tregs) and mucosal-associated invariant T cells (MAITs) within the context of inflammatory bowel disease, primary sclerosing cholangitis, and non-alcoholic steatohepatitis. Tregs are crucial in maintaining peripheral tolerance and preventing autoimmunity. MAIT cells have a unique ability to rapidly recognize microbial metabolites and mount a local immune response and act as a ‘biliary firewall’ at the gut and biliary epithelial barrier. We also outline how current knowledge can be exploited to develop novel therapies to control the propagation of chronic gut- and liver-related inflammatory and autoimmune conditions. We specifically focus on the nature of the Tregs’ cell therapy product and outline an adjunctive role for low-dose IL-2. All in all, it is clear that translational immunology is at crucial crossroads. The success of ongoing clinical trials in cellular therapies for inflammatory gut and liver conditions could revolutionize the treatment of these conditions and the lives of our patients in the coming years.Electronic supplementary materialThe online version of this article (10.1007/s12072-018-9882-x) contains supplementary material, which is available to authorized users.

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“…Several features suggest that liver diseases could be associated with MAIT cell alterations . First, MAIT cells are particularly abundant in the human liver, in which they can represent up to 50% of T cells in healthy individuals.…”

Section: Liver Diseasesmentioning

confidence: 99%

“…Several features suggest that liver diseases could be associated with MAIT cell alterations. 16,61 First, MAIT cells are particularly abundant in the human liver, in which they can represent up to 50% of T cells in healthy individuals. Second, the liver is in contact with bacteria and bacterial compounds drained from the hepatic portal vein in case of leaky gut usually associated with chronic liver diseases of various etiologies, as well as via the bile ducts due to biliary reflux.…”

Section: Liver Diseasesmentioning

confidence: 99%

Mucosal‐associated invariant T cells in autoimmune and immune‐mediated diseases

Rouxel

Lehuen

2018

Immunol Cell Biol

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Autoimmune and inflammatory diseases have complex etiologies not fully understood. Both innate and adaptive immune cells are involved in the pathogenesis of these diseases. Mucosal-associated invariant T (MAIT) cells express an invariant TCRα chain (Vα7.2-Jα33 in humans and Vα19-Jα33 in mice) and recognize the conserved MHC-I-related molecule MR1 presenting bacterial metabolites derived from the synthesis of vitamin B. MAIT cells harbor tissue homing properties and produce inflammatory cytokines, suggesting that MAIT cells may play a key role in autoimmune and inflammatory diseases. In this review, we described the current knowledge on MAIT cells in these pathologies, based on patients analyses as well as mouse models. While most of the studies support a deleterious role of MAIT cells in tissue inflammation and destruction, a few reports suggest a protective role of MAIT cells. MAIT cells could represent a new biomarker of disease progression, and a better knowledge of their function might open new avenues for therapeutic strategies based on their manipulation.

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Lights on MAIT cells, a new immune player in liver diseases

Cited by 14 publications

References 21 publications

Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes

Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes

Linking the gut and liver: crosstalk between regulatory T cells and mucosa-associated invariant T cells

Mucosal‐associated invariant T cells in autoimmune and immune‐mediated diseases

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