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

Rouxel, Ophélie, Da silva, Jennifer, Beaudoin, Lucie, Nel, Isabelle, Tard, Céline, Cagninacci, Lucie, Kiaf, Badr, Oshima, Masaya, Diedisheim, Marc, Salou, Marion, Corbett, Alexandra, Rossjohn, Jamie, McCluskey, James, Scharfmann, Raphael, Battaglia, Manuela, Polak, Michel, Lantz, Olivier, Beltrand, Jacques and Lehuen, Agnès 2017. Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes. Nature Immunology 18 (12) , pp. 1321-1331. 10.1038/ni.3854

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Abstract

Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of pancreatic β-cells by the immune system that involves innate and adaptive immune cells. Mucosal-associated invariant T cells (MAIT cells) are innate-like T-cells that recognize derivatives of precursors of bacterial riboflavin presented by the major histocompatibility complex (MHC) class I–related molecule MR1. Since T1D is associated with modification of the gut microbiota, we investigated MAIT cells in this pathology. In patients with T1D and mice of the non-obese diabetic (NOD) strain, we detected alterations in MAIT cells, including increased production of granzyme B, which occurred before the onset of diabetes. Analysis of NOD mice that were deficient in MR1, and therefore lacked MAIT cells, revealed a loss of gut integrity and increased anti-islet responses associated with exacerbated diabetes. Together our data highlight the role of MAIT cells in the maintenance of gut integrity and the control of anti-islet autoimmune responses. Monitoring of MAIT cells might represent a new biomarker of T1D, while manipulation of these cells might open new therapeutic strategies.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 1529-2908
Date of First Compliant Deposit: 5 January 2018
Date of Acceptance: 13 September 2017
Last Modified: 28 Apr 2018 01:29
URI: http://orca.cf.ac.uk/id/eprint/107934

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