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    Team: Genetics of the immune system and chronic inflammatory rheumatic diseases

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    Team leaders

     

    Immune-mediated diseases comprise a clinically heterogeneous group of diseases affecting about 5% of individuals of European origin. Knowledge of their pathogenic mechanisms has strikingly increased these recent years taking advantage of the huge progresses made in immunogenetics.
    Our research offers a unique opportunity both in basic and in translational approaches to continue the deciphering of immunogenic disorders. Our goal is to link inflammation and immune system with human diseases based on a multidisciplinary approach which involves a two-way process going back and forth between the analysis of the genetic data, the dissection of immunological mechanisms and the potential transfer of the findings to the patient management.

     

    Objectives

     

    Our main research interest is to decipher the molecular mechanisms leading to the establishment of immune tolerance to self and therefore preventing autoimmune manifestations and diseases.

         Three main pillars constitute the organization of the research program within the team: 1) regulation of auto-antigen expression, 2) Genomic analysis of the immune mediated disease with diagnostic, prognostic and therapeutic applications, 3) Functional validation of raised pathways using in vitro and animal models.

    Our ultimate goal is to help development of new diagnostic and therapeutic strategies based on pathophysiological grounds. The interactions between scientists and physicians in the team contribute importantly to the translation of fundamental research into clinical application. 

     

     

     

    Main publicatons

    Terao C, Kawaguchi T, Dieude P, Varga J, Kuwana M, Hudson M, Kawaguchi Y, Matucci-Cerinic M, Ohmura K, Riemekasten G, Kawasaki A, Airo P, Horita T, Oka A, Hachulla E, Yoshifuji H, Caramaschi P, Hunzelmann N, Baron M, Atsumi T, Hassoun P, Torii T, Takahashi M, Tabara Y, Shimizu M, Tochimoto A, Ayuzawa N, Yanagida H, Furukawa H, Tohma S, Hasegawa M, Fujimoto M, Ishikawa O, Yamamoto T, Goto D, Asano Y, Jinnin M, Endo H, Takahashi H, Takehara K, Sato S, Ihn H, Raychaudhuri S, Liao K, Gregersen P, Tsuchiya N, Riccieri V, Melchers I, Valentini G, Cauvet A, Martinez M, Mimori T, Matsuda F, Allanore Y. Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis.Ann Rheum Dis. 2017 Jun;76(6):1150-1158. 

    Avouac J, Konstantinova I, Guignabert C, Pezet S, Sadoine J, Guilbert T, Cauvet A, Tu L, Luccarini JM, Junien JL, Broqua P, Allanore Y. Pan-PPAR agonist IVA337 is effective in experimental lung fibrosis and pulmonary hypertension. Ann Rheum Dis. 2017 76(11):1931-1940

    Ruzehaji N, Frantz C, Ponsoye M, Avouac J, Pezet S, Guilbert T, Luccarini JM, Broqua P, Junien JL, Allanore Y. Pan PPAR agonist IVA337 is effective in prevention and treatment of experimental skin fibrosis. Ann Rheum Dis. 2016 Dec;75(12):2175-2183.

    Ponsoye M, Frantz C, Ruzehaji N, Nicco C, Elhai M, Ruiz B, Cauvet A, Pezet S, Brandely ML, Batteux F, Allanore Y, Avouac J. Treatment with abatacept prevents experimental dermal fibrosis and induces regression of established inflammation-driven fibrosis. Ann Rheum Dis. 2016 Dec;75(12):2142-2149.

    Elhai M, Avouac J, Hoffmann-Vold AM, Ruzehaji N, Amiar O, Ruiz B, Brahiti H, Ponsoye M, Fréchet M, Burgevin A, Pezet S, Sadoine J, Guilbert T, Nicco C, Akiba H, Heissmeyer V, Subramaniam A, Resnick R, Molberg Ø, Kahan A, Chiocchia G, Allanore Y. OX40L blockade protects against inflammation-driven fibrosis. Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):E3901-10.

    Giraud M, Jmari N, Du L, Carallis F, Nieland TJ, Perez-Campo FM, Bensaude O, Root DE, Hacohen N, Mathis D, Benoist C. An RNAi screen for Aire cofactors reveals a role for Hnrnpl in polymerase release and Aire-activated ectopic transcription. Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1491-6.

     

    Team's news

    • The Allanore lab received an Atip/Avenir Grant from the French government [Jan 2013]
    • The The Giraud lab received «Chair of Excellence» Grant from the French government [Jul 2011]