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.

CX3CR1 deficiency promotes muscle repair and regeneration by enhancing macrophage ApoE production / L. Arnold, H. Perrin, C.B. De Chanville, M. Saclier, P. Hermand, L. Poupel, E. Guyon, F. Licata, W. Carpentier, J. Vilar, R. Mounier, B. Chazaud, N. Benhabiles, A. Boissonnas, B. Combadiere, C. Combadiere. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 6:1(2015), pp. 8972.1-8972.12. [10.1038/ncomms9972]

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

Saclier M.;
2015

Abstract

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.
atherosclerotic lesion formation; skeletal-muscle; altered inflammation; fractalkine receptor; cell recruitment; monocyte subsets; CCR2-/-MICE; in-vivo; expression; accumulation
Settore BIO/17 - Istologia
NATURE COMMUNICATIONS
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/735657
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