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Contribution à l'étude de la pathogénèse de la polyarthrite rhumatoïde : analyse des mécanismes régulateurs de la réponse inflammatoire

Abstract : During my PhD, I studied the mechanisms that control inflammation which, when disturbed, can lead to a severe autoimmune/ auto inflammatory disease, rheumatoid arthritis (RA). My work was focused on the analysis of two aspects in these mechanisms: first, I participated to an analysis of the roles of the endonuclease DICER (involved in the biogenesis of microRNAs – miRs) in the pathogenesis of RA, specifically in fibroblast-like synoviocytes (FLS), which are resident cells of the synovial cavity. I also initiated a study aiming at the identification of the FLS transcriptome which is regulated by miRs in RA patients. This approach will provide an overview of the miR-dependent regulation in these cells and enable the identification of in vivo validated miR-targeted mRNAs in RA. A second axis of my thesis project aimed at providing a better description of the intercellular dialogue in the joint cavity. For this, I was particularly interested in the role of plasmacytoid dendritic cells (pDCs) in the pathophysiology of RA. I demonstrated a protective role of these cells (initially described for their functions in antiviral defense) in the context of inflammatory arthritis in several mouse models. During this work, I had the opportunity to try an innovative therapeutic strategy based on the recruitment and activation of pDCs in the joints. This noninvasive and painless approach (topical application of cream containing 5% imiquimod) was effective in reducing inflammatory clinical symptoms and also improved biological markers such as bone erosion.
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Ramzi Nehmar. Contribution à l'étude de la pathogénèse de la polyarthrite rhumatoïde : analyse des mécanismes régulateurs de la réponse inflammatoire. Rhumatologie et système ostéo-articulaire. Université de Strasbourg, 2016. Français. ⟨NNT : 2016STRAJ122⟩. ⟨tel-02918061⟩

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