Résumé :
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Perimuscular connective tissue has been poorly investigated at the cellular level although several inflammatory myopathies may exhibit huge epimysial macrophage infiltration. We examined murine muscle connective tissue in steady state conditions and after an injury. Normal muscle epi/perimysium hosts a dense network of cells mainly composed of fibroblasts and resident macrophages (MPs). Flow cytometry and immumohistochemistry were in keeping with CD45+, CD11b+, F4/80+, CCR2+, and CD206+ resident MPs. After injury, epi/perimysium appeared as a privileged migration pathway for both ingressing and outgoing leukocytes, i.e. mainly monocyte/macrophages (MO/MPs). Using cross-bone marrow transplantation studies to discriminate resident from exsudate MO/MPs, we observed that, rapidly after injury or exposure to TNF-alpha, muscle resident MPs concentrate above the injury site, and selectively release MCP1 and KC chemokines to attract circulating MO/MPs. Loss-of-function experiments were conducted in chimeric mice obtained by bone marrow (BM) transplantation, using Tg:CD11b-DTR mice as recipients and Tg:CAG-GFP mice as donors. In these chimeras diphteric toxin (DT) injection induces selective resident MP depletion without involvement of circulating MOs. After myoinjury, selective resident MP ablation resulted in a dramatic attenuation of exsudate MO/MP infiltration. From 1 to 3 weeks after myoinjury, regardless of its cause, another cell population derived from blood (CD11b+, CD11cint, F4/80+ ) accumulated in the epi/perimysium. These cells were shown to present the antigen similarly to immature bone-marrow derived DCs in the allogenic mixed leucocyte reaction (MLR) assay, which consists in cocultures of the APC with allogenic immature T cells. By both their phenotype and their functional ability to present the antigen, these cells correspond to the recently acknowledged monocyte-derived DC subset. This study points out a critical role for resident epimysial MPs in orchestrating exsudate MO/MPs infiltration, and documents de novo post-injury generation of immature dendritic cells which exact role in physiology and pathology deserves investigation.
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