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

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Arnold, Ludovic | Perrin, Hélène | de Chanville, Camille Baudesson | Saclier, Marielle | Hermand, Patricia | Poupel, Lucie | Guyon, Elodie | Licata, Fabrice | Carpentier, Wassila | Vilar, José | Mounier, Rémi | Chazaud, Bénédicte | Benhabiles, Nora | Boissonnas, Alexandre | Combadiere, Béhazine | Combadiere, Christophe

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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