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Theses

Immunité innée, balance th1/th17 et précurseurs musculaires dans les myopathies inflammatoires

Abstract : This thesis, devoted to the inflammatory myopathies, is demonstrating the potential role in autoimmune disorders of Toll-like receptors (TLRs), gateway between innate and adaptive immune system, and more specifically in muscular diseases the fundamental role of muscle cell it-self. After the presentation of the general clinical features and the immunopathology of inflammatory myopathies, the adaptive immune response is the subject of the second part,demonstrating the abnormal accumulation of mature dendritic cells in myositis muscle, and the presence of Th1 and Th17 cells with a predominant Th1 profile. Innate immune system is next investigated, demonstrating the overexpression of TLR3 and 7 and of C-type lectin receptors characteristic of inflammatory myopathies. In vitro, stimulation of the TLR3 pathway in human myoblasts induces the production of IL6 and of the βchemokine CCL20, which in turn participate to the differentiation and the migration of T cells and dendritic cells, and of IFNβ which contributes to HLA class I up-regulation. The expression of TLR3 is differentially regulated by Th1 and Th17 cytokines. Finally, this work strongly implicates immature myoblast precursors in the pathogenesis of inflammatory myopathies. In contrast to normal muscle tissue, myositis tissue is characterized by the overexpression of HLA class I antigens, TLR3 and TLR7, myositis autoantigens, and IFNβ, all observed in immature myoblast precursors. By focusing damage onto those cells accomplishing repair, a feedforward loop of tissue damage is induced and could explain the defective repair in muscle in addition to the autoimmune attack.
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Anne Tournadre. Immunité innée, balance th1/th17 et précurseurs musculaires dans les myopathies inflammatoires. Sciences agricoles. Université Claude Bernard - Lyon I, 2010. Français. ⟨NNT : 2010LYO10247⟩. ⟨tel-00715926⟩

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