MAIT Cells pp 283-297 | Cite as

MAIT Cells in Type 1 Diabetes Mouse Models

  • Isabelle Nel
  • Lucie Beaudoin
  • Agnès LehuenEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 2098)


MAIT cells are unconventional T cells expressing a semi-invariant αβ TCR, and they recognize bacterial metabolites via the highly conserved MR1 protein. MAIT cells interact with gut microbiota and literature reports alterations of gut homeostasis in type 1 diabetes (T1D), suggesting the involvement of MAIT cells in T1D. Since NOD mice is a well-established mouse model of T1D, MAIT cells were studied in these mice to evaluate their potential involvement in disease development. This chapter describes the material and methods required to characterize MAIT cells and to determine their function in T1D mouse models.

Key words

MAIT MR1 T1D NOD Intestinal microbiota Migration Cytokine Activation 



We thank M. Salou for help in analysis of in vitro MAIT cell activation (5-OP-RU/fecal supernatant dilution); the mouse and Cybio facilities of the Cochin Institute. This work was supported by grants from INSERM, CNRS, Laboratoire d’Excellence consortium Inflamex ANR-11-IDEX-0005-02, and the Fondation pour la Recherche Médicale (FRM grant number DEQ20140329520, EQU201903007779 to A.L.), Fondation Francophone pour la Recherche sur le Diabète to A.L., EFSD/JDRF/Lilly to A.L., Aide aux Jeunes Diabétiques fellowship to I.N., Agence National de la Recherche (ANR-17-CE14-0002-01 Diab1MAIT to A.L.).

Author Contributions: I.N. and L.B. wrote the review and A.L. supervised the writing of the review.


  1. 1.
    McWilliam HEG, Birkinshaw RW, Villadangos JA, McCluskey J, Rossjohn J (2015) MR1 presentation of vitamin B-based metabolite ligands. Curr Opin Immunol 34:28–34CrossRefGoogle Scholar
  2. 2.
    Ussher JE, Klenerman P, Willberg CB (2014) Mucosal-associated invariant T-cells: new players in anti-bacterial immunity. Front Immunol 5:450CrossRefGoogle Scholar
  3. 3.
    Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V, Tilloy F et al (2003) Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422(6928):164–169CrossRefGoogle Scholar
  4. 4.
    Lantz O, Legoux F (2018) MAIT cells: an historical and evolutionary perspective. Immunol Cell Biol 96(6):564–572CrossRefGoogle Scholar
  5. 5.
    Lamichhane R, Ussher JE (2017) Expression and trafficking of MR1. Immunology 151(3):270–279CrossRefGoogle Scholar
  6. 6.
    Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B, Liu L et al (2012) MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491(7426):717–723CrossRefGoogle Scholar
  7. 7.
    Kjer-Nielsen L, Corbett AJ, Chen Z, Liu L, Mak JY, Godfrey DI et al (2018) An overview on the identification of MAIT cell antigens. Immunol Cell Biol 96(6):573–587CrossRefGoogle Scholar
  8. 8.
    Corbett AJ, Eckle SBG, Birkinshaw RW, Liu L, Patel O, Mahony J et al (2014) T-cell activation by transitory neo-antigens derived from distinct microbial pathways. Nature 509(7500):361–365CrossRefGoogle Scholar
  9. 9.
    Rahimpour A, Koay HF, Enders A, Clanchy R, Eckle SBG, Meehan B et al (2015) Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers. J Exp Med 212(7):1095–1108CrossRefGoogle Scholar
  10. 10.
    Reantragoon R, Corbett AJ, Sakala IG, Gherardin NA, Furness JB, Chen Z et al (2013) Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells. J Exp Med 210(11):2305–2320CrossRefGoogle Scholar
  11. 11.
    Rouxel O, Da Silva J, Beaudoin L, Nel I, Tard C, Cagninacci L et al (2017) Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes. Nat Immunol 18(12):1321–1331CrossRefGoogle Scholar
  12. 12.
    Soudais C, Samassa F, Sarkis M, Le Bourhis L, Bessoles S, Blanot D et al (2015) In vitro and in vivo analysis of the gram-negative bacteria-derived riboflavin precursor derivatives activating mouse MAIT cells. J Immunol (Baltimore, MD, 1950) 194(10):4641–4649CrossRefGoogle Scholar
  13. 13.
    Rouxel O, Lehuen A (2018) Mucosal-associated invariant T cells in autoimmune and immune-mediated diseases. Immunol Cell Biol 96(6):618–629CrossRefGoogle Scholar
  14. 14.
    Touch S, Assmann KE, Aron-Wisnewsky J, Marquet F, Rouault C, Fradet M et al (2018) Mucosal-associated invariant T (MAIT) cells are depleted and prone to apoptosis in cardiometabolic disorders. FASEB J Off Publ Fed Am Soc Exp Biol. Scholar
  15. 15.
    Magalhaes I, Pingris K, Poitou C, Bessoles S, Venteclef N, Kiaf B et al (2015) Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients. J Clin Invest 125(4):1752–1762CrossRefGoogle Scholar
  16. 16.
    Hegde P, Weiss E, Paradis V, Wan J, Mabire M, Sukriti S et al (2018) Mucosal-associated invariant T cells are a profibrogenic immune cell population in the liver. Nat Commun 9(1):2146CrossRefGoogle Scholar
  17. 17.
    Atkinson MA, Eisenbarth GS, Michels AW (2014) Type 1 diabetes. Lancet Lond Engl 383(9911):69–82CrossRefGoogle Scholar
  18. 18.
    Lehuen A, Diana J, Zaccone P, Cooke A (2010) Immune cell crosstalk in type 1 diabetes. Nat Rev Immunol 10(7):501–513CrossRefGoogle Scholar
  19. 19.
    Bluestone JA, Herold K, Eisenbarth G (2010) Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 464(7293):1293–1300CrossRefGoogle Scholar
  20. 20.
    Anderson MS, Bluestone JA (2005) The NOD mouse: a model of immune dysregulation. Annu Rev Immunol 23:447–485CrossRefGoogle Scholar
  21. 21.
    Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC et al (2008) Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455(7216):1109–1113CrossRefGoogle Scholar
  22. 22.
    Kostic AD, Gevers D, Siljander H, Vatanen T, Hyötyläinen T, Hämäläinen A-M et al (2015) The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe 17(2):260–273CrossRefGoogle Scholar
  23. 23.
    Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F et al (2006) Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes 55(5):1443–1449CrossRefGoogle Scholar
  24. 24.
    Alam C, Bittoun E, Bhagwat D, Valkonen S, Saari A, Jaakkola U et al (2011) Effects of a germ-free environment on gut immune regulation and diabetes progression in non-obese diabetic (NOD) mice. Diabetologia 54(6):1398–1406CrossRefGoogle Scholar
  25. 25.
    Franciszkiewicz K, Salou M, Legoux F, Zhou Q, Cui Y, Bessoles S et al (2016) MHC class I-related molecule, MR1, and mucosal-associated invariant T cells. Immunol Rev 272(1):120–138CrossRefGoogle Scholar
  26. 26.
    Koay H-F, Gherardin NA, Enders A, Loh L, Mackay LK, Almeida CF et al (2016) A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage. Nat Immunol 17(11):1300–1311CrossRefGoogle Scholar
  27. 27.
    Le Bourhis L, Martin E, Péguillet I, Guihot A, Froux N, Coré M et al (2010) Antimicrobial activity of mucosal-associated invariant T cells. Nat Immunol 11(8):701–708CrossRefGoogle Scholar
  28. 28.
    Shimamura M, Huang Y-Y, Goji H, Endo S, Migishima R, Yokoyama M (2011) Regulation of immunological disorders by invariant Vα19-Jα33 TCR-bearing cells. Immunobiology 216(3):374–378CrossRefGoogle Scholar
  29. 29.
    Eckle SBG, Birkinshaw RW, Kostenko L, Corbett AJ, McWilliam HEG, Reantragoon R et al (2014) A molecular basis underpinning the T cell receptor heterogeneity of mucosal-associated invariant T cells. J Exp Med 211(8):1585–1600CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Isabelle Nel
    • 1
    • 2
    • 3
  • Lucie Beaudoin
    • 1
    • 2
    • 3
  • Agnès Lehuen
    • 1
    • 2
    • 3
    Email author
  1. 1.INSERM U1016, Institut CochinParisFrance
  2. 2.CNRS, UMR8104ParisFrance
  3. 3.Université Paris Descartes, Laboratoire d’Excellence Inflamex, Sorbonne Paris CitéParisFrance

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