Journal article

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

Amine Toubal, Badr Kiaf, Lucie Beaudoin, Lucie Cagninacci, Moez Rhimi, Blandine Fruchet, Jennifer da Silva, Alexandra J Corbett, Yannick Simoni, Olivier Lantz, Jamie Rossjohn, James McCluskey, Philippe Lesnik, Emmanuelle Maguin, Agnes Lehuen

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2020

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 dysb..

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Grants

Awarded by Laboratory of Excellence INFLAMEX


Awarded by Fondation pour la Recherche Medicale


Awarded by project CMCU-PHC Utique


Awarded by Campus France



Funding Acknowledgements

We are grateful to Ute Rogner for critical reading of the paper. We thank the animals facilities from Cochin Institut and Pitie Salpetriere Hospital, Cybio and HistIM facilities from Cochin Institute; Gerard Eberl, Institut Pasteur, Paris, for the ROR gamma t-GFP C57BL/6; the National Institutes of Health tetramer core facility for mouse MR1 tetramers; Amine Jablaoui and Aicha Kriaa for technical and methodology support and A. Gargouri for support. A.T., B.K., and A.L. are supported by ANR-11-IDEX-0005-02 Laboratory of Excellence INFLAMEX; A.T. was also supported by RHU QUID-NASH; B.K. was also supported by the Fondation pour la Recherche Medicale; E.M. is supported by the project CMCU-PHC Utique (no. 14G0816)-Campus France (no. 30666QM). A.L. is supported by ANR-14-CE12-0018, ANR-15-CE14-0029-03, ANR-19-CE14-0020, the Societe Francophone de Diabetologie, Fondation Francophone pour la Recherche sur le Diabete, Fondation pour la Recherche Medicale (EQU201903007779) and the European Foundation for the Study of Diabetes to A.L. and A.T. Servier Medical Art for the free medical images (licensed under a Creative Commons Attribution 3.0 Unported License).