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

Ophélie Rouxel, Jennifer Da Silva, Lucie Beaudoin, Isabelle Nel, Céline 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, Agnès 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.

Original languageEnglish
Pages (from-to)1321-1331
Number of pages11
JournalNature Immunology
Volume18
Issue number12
DOIs
Publication statusPublished - 16 Nov 2017

Keywords

  • autoimmunity
  • mucosal immunology

Cite this

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

Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes. / Rouxel, Ophélie; Da Silva, Jennifer; Beaudoin, Lucie; Nel, Isabelle; Tard, Céline; Cagninacci, Lucie; Kiaf, Badr; Oshima, Masaya; Diedisheim, Marc; Salou, Marion; Corbett, Alexandra; Rossjohn, Jamie; McCluskey, James; Scharfmann, Raphael; Battaglia, Manuela; Polak, Michel; Lantz, Olivier; Beltrand, Jacques; Lehuen, Agnès.

In: Nature Immunology, Vol. 18, No. 12, 16.11.2017, p. 1321-1331.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Rouxel, Ophélie

AU - Da Silva, Jennifer

AU - Beaudoin, Lucie

AU - Nel, Isabelle

AU - Tard, Céline

AU - Cagninacci, Lucie

AU - Kiaf, Badr

AU - Oshima, Masaya

AU - Diedisheim, Marc

AU - Salou, Marion

AU - Corbett, Alexandra

AU - Rossjohn, Jamie

AU - McCluskey, James

AU - Scharfmann, Raphael

AU - Battaglia, Manuela

AU - Polak, Michel

AU - Lantz, Olivier

AU - Beltrand, Jacques

AU - Lehuen, Agnès

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N2 - 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.

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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 Nov 16;18(12):1321-1331. https://doi.org/10.1038/ni.3854