CX3CR1 deficiency promotes muscle repair and regeneration by enhancing macrophage ApoE production

作者：Ludovic Arnold, Hélène Perrin, Camille Baudesson de Chanville, Marielle Saclier, Patricia Hermand, Lucie Poupel, Elodie Guyon, Fabrice Licata, Wassila Carpentier, José Vilar, Rémi Mounier, Bénédicte Chazaud, Nora Benhabilès, Alexandre Boissonnas, Béhazine Combadière, Christophe Combadière · 发表于：Nature Communications · 年份：2015 · DOI：10.1038/ncomms9972 · 被引用次数：74 · 研究领域：Chemokine receptors and signaling、Immune cells in cancer、Protease and Inhibitor Mechanisms

Muscle injury triggers inflammation in which infiltrating mononuclear phagocytes are crucial for tissue regeneration. The interaction of the CCL2/CCR2 and CX3CL1/CX3CR1 chemokine axis that guides phagocyte infiltration is incompletely understood. Here, we show that CX3CR1 deficiency promotes muscle repair and rescues Ccl2(-/-) mice from impaired muscle regeneration as a result of altered macrophage function, not infiltration. Transcriptomic analysis of muscle mononuclear phagocytes reveals that Apolipoprotein E (ApoE) is upregulated in mice with efficient regeneration. ApoE treatment enhances phagocytosis by mononuclear phagocytes in vitro, and restores phagocytic activity and muscle regeneration in Ccl2(-/-) mice. Because CX3CR1 deficiency may compensate for defective CCL2-dependant monocyte recruitment by modulating ApoE-dependent macrophage phagocytic activity, targeting CX3CR1 expressed by macrophages might be a powerful therapeutic approach to improve muscle regeneration.