Journal article

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

Ophelie Rouxel, Jennifer Da Silva, Lucie Beaudoin, Isabelle Nel, Celine Tard, Lucie Cagninacci, Badr Kiaf, Masaya Oshima, Marc Diedisheim, Marion Salou, Alexandra Corbett, Jamie Rossjohn, James McCluskey, Raphael Scharfmann, Manuela Battaglia, Michel Polak, Olivier Lantz, Jacques Beltrand, Agnes Lehuen

NATURE IMMUNOLOGY | NATURE PUBLISHING GROUP | Published : 2017

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 di..

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Grants

Awarded by Agence Nationale de la Recherche


Awarded by Fondation pour la Recherche Medicale


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Funding Acknowledgements

We thank all the patients and the medical staff of Necker hospital; A. Toubal for critical reading of the manuscript; F. Letourneur and A. Stabilini for technical help; the mouse, Cybio and HistIM facilities of the Cochin Institute; G, Eberl (Institut Pasteur, Paris) for the bacterial artificial chromosome expressing ROR gamma t-GFP; the US National Institutes of Health tetramer core facility; and H. Fohrer-Ting, R. Porcher and M. Laanani for help in statistical analyses. Supported by the Societe Francophone de Diabetologie (R.S.), the Foundation Bettencourt Schueller (R.S.), the Laboratoire d'Excellence REVIVE (R.S.), Fondation pour la Recherche Medicale (C.T., M.O. and M.D.), Type 1 Diabetes TrialNet (M.B.), Agence Nationale de la Recherche (NR-11-IDEX-0005-02 Laboratory of Excellence INFLAMEX to A.L.), Fondation pour la Recherche Medicale (DEQ20140329520 to A.L.), the INSERM crosscutting program on microbiota (A.L.), the European Foundation for the Study of Diabetes-Juvenile Diabetes Research Foundation-Lilly (A.L.), the Departement Hospitalo-Universitaire on Autoimmune and Hormonal Diseases (A.L.), the Ministry of Research (O. R.) and Aide aux Jeunes Diabetiques (I.N.).