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

O Rouxel, J Da Silva, L Beaudoin, I Nel, C Tard, L Cagninacci, B Kiaf, M Oshima, M Diedisheim, M Salou, A Corbett, J Rossjohn, J McCluskey, R Scharfmann, M Battaglia, M Polak, O Lantz, J Beltrand, A Lehuen

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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. © 2017 Nature America Inc,part of Springer Nature. All rights reserved.
Original languageEnglish
Pages (from-to)1321-1331
Number of pages11
JournalNature Immunology
Volume18
Issue number12
DOIs
Publication statusPublished - 2017

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Type 1 Diabetes Mellitus
Inbred NOD Mouse
Granzymes
Riboflavin
Major Histocompatibility Complex
Autoimmunity
Autoimmune Diseases
Mucosal-Associated Invariant T Cells
Immune System
Biomarkers
Maintenance
Pathology
T-Lymphocytes

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Rouxel, O., Da Silva, J., Beaudoin, L., Nel, I., Tard, C., Cagninacci, L., ... Lehuen, A. (2017). Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes. Nature Immunology, 18(12), 1321-1331. https://doi.org/10.1038/ni.3854

Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes. / Rouxel, O; Da Silva, J; Beaudoin, L; Nel, I; Tard, C; Cagninacci, L; Kiaf, B; Oshima, M; Diedisheim, M; Salou, M; Corbett, A; Rossjohn, J; McCluskey, J; Scharfmann, R; Battaglia, M; Polak, M; Lantz, O; Beltrand, J; Lehuen, A.

In: Nature Immunology, Vol. 18, No. 12, 2017, p. 1321-1331.

Research output: Contribution to journalArticle

Rouxel, O, Da Silva, J, Beaudoin, L, Nel, I, Tard, C, Cagninacci, L, Kiaf, B, Oshima, M, Diedisheim, M, Salou, M, Corbett, A, Rossjohn, J, McCluskey, J, Scharfmann, R, Battaglia, M, Polak, M, Lantz, O, Beltrand, J & Lehuen, A 2017, 'Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes', Nature Immunology, vol. 18, no. 12, pp. 1321-1331. https://doi.org/10.1038/ni.3854
Rouxel O, Da Silva J, Beaudoin L, Nel I, Tard C, Cagninacci L et al. Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes. Nature Immunology. 2017;18(12):1321-1331. https://doi.org/10.1038/ni.3854
Rouxel, O ; Da Silva, J ; Beaudoin, L ; Nel, I ; Tard, C ; Cagninacci, L ; Kiaf, B ; Oshima, M ; Diedisheim, M ; Salou, M ; Corbett, A ; Rossjohn, J ; McCluskey, J ; Scharfmann, R ; Battaglia, M ; Polak, M ; Lantz, O ; Beltrand, J ; Lehuen, A. / Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes. In: Nature Immunology. 2017 ; Vol. 18, No. 12. pp. 1321-1331.
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AB - 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. © 2017 Nature America Inc,part of Springer Nature. All rights reserved.

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