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    The role of innate-like T cells in the regulation T1D

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    Principal investigator: Agnès Lehuen
    Contact : agnes.lehuen@inserm.fr – Phone : +33 1 76 53 55 90  

    Co-investigator: Jacques Beltrand

    Contact : jacques.beltrand@aphp.fr ; jacques.beltrand@inserm.fr - Phone + 33 1 44 48 15 45

     

    Objective

     MAIT cells in T1D diabetes. We wish to determine the role of innate-like T cells in the regulation of both T1D. Natural killer T (NKT) cells and Mucosal Associated Invariant T (MAIT) cells are non-conventional T cells that recognized lipid antigens and vitamin metabolites, respectively. As such they play a critical role as sensors of metabolic abnormalities. Importantly these innate-like T cells can regulate both innate and adaptive immunity. MAIT cells are present in various tissues and more particularly in the liver and the gut, where they are activated by bacterial ligands. Due to the impact of microbiota in the development of T1D, we are presently analyzing the role of MAIT cells in this pathology. The studies are performed in patients as well as in mouse models.

     

     

    The group

     Lucie Beaudoin-Desmarest, (Engineer, INSERM), Leo Bertrand (Master student, ENS), Jacques Beltrand (Assistant professor and paediatric diabetologist, APHP), Isabelle Nel (Doctoral student, INSERM), Carol Passone (Post-doctoral fellow, ISPAD-JDRF), Matthieu Roulard (Doctoral student, University PARIS V), Camille Rousseau (Engineer Assistant, INSERM)

     

    Research interests

    In T1D patients, circulating MAIT cells are significantly decreased, and their activation status is more pronounced in young children. We have generated non-obese diabetic (NOD) mice devoid of MAIT cells (MR1-/-), as well as transgenic NOD mice exhibiting high MAIT cell frequency. Our data in murine models revealed a protective role of MAIT cells against the development of T1D. MAIT cells play a pivotal role in the maintenance of the gut integrity

    thereby dampening the autoimmune response. In parallel to the murine studies we are analysing MAIT cells in different cohorts of T1D patients.

     

     

    Main publications and patents

    1 : Rouxel O, Lehuen A. Mucosal-associated invariant T cells in autoimmune and immune-mediated diseases. Review. Immunology & Cell Biology 2018 Jul;96(6):618-629.

    2 : 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.  Nature Immunology 2017 Dec;18(12):1321-1331.

    3 : Nel, I., Lehuen, A. Defective Invariant Natural Killer T-Cell Suppression in Patients With Type 1 Diabetes. Diabetes 2016; 65(8):2121-3.

    4 : Lehuen, A. A double-edged sword against type 1 diabetes. N Engl J Med 2015; 372(8):778-80.

    5 : Ghazarian, L., Simoni, Y., Magalhaes, I., Lehuen, A. Invariant NKT cell development: focus on NOD mice. Curr Opin Immunol 2014; 27C:83-88.

    6 : Beaudoin, L., Diana, J., Ghazarian, L., Simoni, Y., Boitard, C., Lehuen, A. Plasmacytoid dendritic cells license regulatory T cells, upon iNKT-cell stimulation, to prevent autoimmune diabetes. Eur J Immunol 2014; 44(5):1454-66.

    7 : Ghazarian, L., Diana, J., Beaudoin, L., Larsson, P. G., Puri, R. K., van Rooijen, N., Flodstrom-Tullberg, M., Lehuen, A. Protection Against Type 1 Diabetes Upon Coxsackievirus B4 Infection and iNKT-Cell Stimulation: Role of Suppressive Macrophages. Diabetes 2013; 62(11):3785-96.

    8 : Methods and kits of assessing status, risk or prognosis of type 1 diabetes. WO 2017/162759, the 22nd March 2017  J. Da Silva, I. Nel, L. Beaudoin, A. Lehuen

     

    Financial supports

    These programs are supported by: Agence Nationale de la Recherche: Labex INFLAMEX, Fondation pour la Recherche Médicale, Ministère de l’enseignement supérieur et de la recherche, Fondation Francophone pour la Recherche sur le Diabète,  European Association for the study of diabetes, INSERM, CNRS.