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Nat Immunol. 2017 Dec;18(12):1321-1331. doi: 10.1038/ni.3854. Epub 2017 Oct 9.

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

Rouxel O1,2,3, Da Silva J1,2,3, Beaudoin L1,2,3, Nel I1,2,3, Tard C1,2,3, Cagninacci L1,2,3, Kiaf B1,2,3, Oshima M1,2, Diedisheim M1,2, Salou M4, Corbett A5, Rossjohn J6,7,8, McCluskey J5, Scharfmann R1,2, Battaglia M9, Polak M1,2,10,11, Lantz O4, Beltrand J1,2,10,11, Lehuen A1,2,3.

Author information

1
INSERM U1016, Institut Cochin, Paris, France, and Université Paris Descartes, Paris, France.
2
CNRS, UMR8104, Paris, France.
3
Laboratoire d'Excellence INFLAMEX, Sorbonne Paris Cité, Paris, France.
4
INSERM U932, Institut Curie, Paris, France.
5
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
6
ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia.
7
Institute of Infection and Immunity, Cardiff University, Cardiff, UK.
8
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia.
9
Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy, and TrialNet Clinical Center, San Raffaele Hospital, Milan, Italy.
10
Service Endocrinologie, Gynécologie et Diabétologie Pédiatrique, Hôpital Universitaire Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
11
Faculté de Médecine Paris Descartes, Université Sorbonne Paris Cité, Paris, France.

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.

PMID:
28991267
PMCID:
PMC6025738
DOI:
10.1038/ni.3854
[Indexed for MEDLINE]
Free PMC Article

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