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    Team: Pathogenesis and innovative therapies in systemic sclerosis and chronic fibro-inflammatory diseases

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    Objectives

    Systemic sclerosis (SSc), a multisystem autoimmune connective tissue disease, has the highest mortality from all inflammatory rheumatological disorders and a heavy morbidity. Its pathogenesis is incompletely understood but it is thought to occur because of interactions between susceptibility genes and environmental factors. The interplay between microvascular damages and both innate and adaptative immune disturbances promotes activation of mesenchymal cells that induce fibrosis. Our group is committed to decipher SSc pathogenesis since many years. Our strategies include genetic susceptibility, polarization of innate and adaptative immune responses, role of reactive oxygen species in the interplay between various systems, epigenetic marks contributing to fibroblast dysfunction and chronic inflammation,  with the ultimate goal to develop biomarkers and new therapies. We have established a huge databank of DNA, mRNA, serum, plasma, tissues and cells to perform translational research.  Moreover, we have established a pre-clinical platform of SSc related and complementary animal models to investigate in vivo any relevant candidate as a potential treatment. These strategies are further applied in other fibro-inflammatory diseases with key interest in rheumatoid arthritis and endometriosis thanks to the expertise and recruitment at Cochin University Hospital.

     

    Main Publications

    1. Kavian N, Mehlal S, Jeljeli M, Saidu NEB, Nicco C, Cerles O, Chouzenoux S, Cauvet A, Camus C, Ait-Djoudi M, Chéreau C, Kerdine-Römer S, Allanore Y, Batteux F. The Nrf2-Antioxidant Response Element Signaling Pathway Controls Fibrosis and Autoimmunity in Scleroderma. Front Immunol. 2018 Aug 16;9:1896
    2. 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 Nov;76(11):1931-1940.
    3. 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.
    4. 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. 
    5. Morin F, Kavian N, Nicco C, Cerles O, Chéreau C, Batteux F. Improvement of Sclerodermatous Graft-Versus-Host Disease in Mice by Niclosamide. J Invest Dermatol. 2016 Nov;136(11):2158-2167

     

     Team’s news

     

    • Pr Jérome Avouac did present some data at the last American College of Rheumatology meeting (Chicago October 2018)
    • SEUD meeting 16-18 May 2019 (Montreal) – C Chapron, Board
    • Paris Redox World Congress 20-21 June 2019 – F Batteux, Chaiman, C Nicco, Board
    • Journée JC Dreyfus. ROS in physiology & diseases. Sept 2019– F Batteux, Chaiman

     

     

    Contacts

    Institut Cochin
    INSERM U1016, CNRS UMR 8104, Université Paris Descartes
    Bâtiment Gustave Roussy - 4ème étage
    27, rue du Faubourg St Jacques
    75014 Paris, France
    Tél : +33140516517
    Fax : +33140516641

     

     

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