Résumé :
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Etiopathogenesis of sarcoidosis, a systemic granulomatous disease, still remains obscure. A multitude of organs affected by systemic sarcoidosis have been described. Skeletal muscles may also be affected, leading to myalgia and weakness. A work-up of the specific immune response with emphasis on the macrophage response is provided. Affected muscle tissue, obtained from 7 patients with systemic sarcoidosis was analyzed in comparison to 7 other myopathies, containing macrophagocytic infiltration. Immune cells were characterized by immunohistochemistry, and the mediators involved were assessed by qPCR.We point out that monocytes/macrophages and giant cells within granulomas of muscle tissue from sarcoidosis patients show a status of alternative activation (M2) based on their expression of CD206, CD301, arginase-1, and SOCS-1, as a consequence of a functionally Th2-biased cytokine profile. Significant fibrosis, and upregulation of CCL18 were associated with M2 macrophages. Conversely, upregulated Th1 cytokines did not result in significant classical activation of macrophages (M1) with poor iNOS and cox2 production. Giant cell formation was further associated with upregulated DAP12 expression.Functionally, alternative activation of macrophages on the basis of a Th2-biased immune response may induce clinical symptoms, and chronic evolution of neuromuscular sarcoidosis. This is the first characterization of Th2-mediated immune mechanisms in neuromuscular sarcoidosis suggesting that a specific macrophage activation status leading to myofibrosis may be a key event in the pathogenesis of this disease.
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