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Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity

Toubal, Amine, Kiaf, Badr, Beaudoin, Lucie, Cagninacci, Lucie, Rhimi, Moez, Fruchet, Blandine, da Silva, Jennifer, Corbett, Alexandra J., Simoni, Yannick, Lantz, Olivier, Rossjohn, Jamie, McCluskey, James, Lesnik, Philippe, Maguin, Emmanuelle and Lehuen, Agnès 2020. Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity. Nature Communications 11 (1) , 3755. 10.1038/s41467-020-17307-0

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Abstract

Obesity is associated with low-grade chronic inflammation promoting insulin-resistance and diabetes. Gut microbiota dysbiosis is a consequence as well as a driver of obesity and diabetes. Mucosal-associated invariant T cells (MAIT) are innate-like T cells expressing a semi-invariant T cell receptor restricted to the non-classical MHC class I molecule MR1 presenting bacterial ligands. Here we show that during obesity MAIT cells promote inflammation in both adipose tissue and ileum, leading to insulin resistance and impaired glucose and lipid metabolism. MAIT cells act in adipose tissue by inducing M1 macrophage polarization in an MR1-dependent manner and in the gut by inducing microbiota dysbiosis and loss of gut integrity. Both MAIT cell-induced tissue alterations contribute to metabolic dysfunction. Treatment with MAIT cell inhibitory ligand demonstrates its potential as a strategy against inflammation, dysbiosis and metabolic disorders.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Publisher: Nature Research
ISSN: 2041-1723
Date of First Compliant Deposit: 20 August 2020
Date of Acceptance: 23 June 2020
Last Modified: 21 Aug 2020 13:00
URI: http://orca.cf.ac.uk/id/eprint/134299

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