Biomedical research institute
     
    You are here: Home / Departments / Endocrinology, Metabolism and Diabetes / Team A. Lehuen / The role of innate-like T cells in the regulation of T2D

    The role of innate-like T cells in the regulation of T2D, obesity an non-alcoholic liver steatosis

    •  

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

    Co- investigators : Ute Christine Rogner and Amine Toubal
    Contact : ute.rogner@inserm.fr – Phone : +33 1 76 53 55 89
    Contact : amine.toubal@inserm.fr – Phone : +33 1 76 53 55 95

     

    Objectives

     1. MAIT cells in T2D diabetes, obesity and nonalcoholic liver steatosis.

    Converging data highlight the role of innate-like T cells, such as NKT and MAIT (Mucosal Associated Invariant T) cells, which represent a first line of T responder lymphocytes controlling the fate of immune responses. The potential role of the gut microbiota in metabolic and liver diseases led us to investigate the MAIT cells that recognized bacterial ligands and are preferably located in the intestinal mucosa and the liver. We are investigating the potential link between MAIT cells, inflammation and dysbiosis in obesity and liver disease using human samples and animal models. Our goal is to determine whether MAIT cell alterations are causal with the goal of developing innovative strategies based on MAIT cell manipulation.

    The group

    Lucie Beaudoin-Desmaret (Engineer, INSERM), Lucie Cagninacci, (Engineer Assistant, INSERM), Blandine Fuchet (Master student, INSERM), Zouriatou Gouda (Engineer, INSERM), Ute C. Rogner (Research Director, CNRS), Camille Rousseau (Engineer Assistant, INSERM), Amine Toubal (Post-doctoral fellow, INSERM).

     

    Research interests

    1. In T2D and obese patients circulating MAIT cells are altered and produce high levels of inflammatory cytokines (e.g. IL-17) in the adipose tissue. We have developed mouse models expressing various frequencies of MAIT cells and we are analysing the impact of MAIT cells on insulin resistance and glucose intolerance, associated with increased inflammation in adipose tissue and the intestine. In parallel we continue studies in T2D and obese patients.

    2. We have developed mouse models that are invalidated for the circadian gene Arntl2 (Bmal2) and address the question if the resulting increase in immune activation contributes to diabetes and obesity.

     

     

    Main publications and patents

    1. Hegde P, Weiss E, Paradis V, Wan J, Mabire M, Sukriti S, Rautou PE,Albuquerque M, Picq O, Gupta AC, Ferrere G, Gilgenkrantz H, Kiaf B, Toubal A, Beaudoin L, Lettéron P, Moreau R, Lehuen A*, Lotersztajn S*. (*equal last authors) Mucosal-associated invariant T cells are a profibrogenic immune cell population in the liver. Nature Communications 2018 Jun 1;9(1):2146. doi: 10.1038/s41467-018-04450-y.
    2. Touch, S., Assmann, K. E., Aron-Wisnewsky, J., Marquet, F., Rouault, C., Fradet, M., Mosbah, H., Consortium, M., Isnard, R., Helft, G., Lehuen, A., Poitou, C., Clement, K., Andre, S., MetaCardis, Consortium Mucosal-associated invariant T (MAIT) cells are depleted and prone to apoptosis in cardiometabolic disorders. FASEB J 2018; 32(9):5078-89. doi: 10.1096/fj.201800052RR.
    3. Toubal, A., Lehuen, A. Lights on MAIT cells, a new immune player in liver diseases. J Hepatol 2016; 64(5):1008-10. doi: 10.1016/j.jhep.2016.02.003.
    4. Lebailly, B., Boitard, C., Rogner, U. C. Circadian rhythm-related genes: implication in autoimmunity and type 1 diabetes. Diabetes Obes Metab 2015; 17 Suppl 1:134-8. doi: 10.1111/dom.12525.
    5. Magalhaes I, Pingris K, Poitou C, Bessoles S, Venteclef N, Kiaf B, Beaudoin L, Da Silva J, Allatif O, Rossjohn J, Kjer-Nielsen L, McCluskey J, Ledoux S, Genser  L, Torcivia A, Soudais C, Lantz O, Boitard C, Aron-Wisnewsky J, Larger E, Clément K, Lehuen A. Mucosal-associated invariant T cell alterations in obese and type 2  diabetic patients. Journal of Clinical Investigation 2015 Apr;125(4):1752-62. doi: 10.1172/JCI78941.
    6. Magalhaes, I., Kiaf, B., Lehuen, A. iNKT and MAIT Cell Alterations in Diabetes. Front Immunol 2015; 6:341. doi: 10.3389/fimmu.2015.00341.
    7. Methods and pharmaceutical compositions for the treatment fibrosis with agents capable of inhibiting the activation of mucosal-associated invariant (MAIT) cells. PCT/FR2017/0, the 22nd June 2017 P. Hegde, E. Weiss, V. Paradis, A. Lehuen, S. Lotersztajn

     

    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.