title: CX3CR1 deficiency promotes muscle repair and regeneration by enhancing macrophage ApoE production.
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.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, U1135, CNRS, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Boulevard de l'Hôpital, F-75013 Paris, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Arnold
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, U1135, CNRS, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Boulevard de l'Hôpital, F-75013 Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Perrin
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, U1135, CNRS, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Boulevard de l'Hôpital, F-75013 Paris, France.
authors.forename: Camille Baudesson
authors.initials: CB
authors.lastname: de Chanville
authors.affiliation: Inserm, U1016, Institut Cochin, 22 Rue Méchain, F-75014 Paris, France.|CNRS, UMR8104, 22 Rue Méchain, F-75014 Paris, France.|University of Paris Descartes, Sorbonne Paris Cite, F-75006 Paris, France.
authors.forename: Marielle
authors.initials: M
authors.lastname: Saclier
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, U1135, CNRS, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Boulevard de l'Hôpital, F-75013 Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hermand
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, U1135, CNRS, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Boulevard de l'Hôpital, F-75013 Paris, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Poupel
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, U1135, CNRS, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Boulevard de l'Hôpital, F-75013 Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Guyon
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, U1135, CNRS, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Boulevard de l'Hôpital, F-75013 Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Licata
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Plateforme Post-Génomique de la Pitié-Salpêtrière (P3S), UMS2 Omique, INSERM US029, 91 Boulevard de l'Hôpital, F-75013 Paris, France.
authors.forename: Wassila
authors.initials: W
authors.lastname: Carpentier
authors.affiliation: Paris Centre de Recherche Cardiovasculaire (PARCC) - HEGP, 56 Rue Leblanc, F-75015 Paris, France.
authors.forename: José
authors.initials: J
authors.lastname: Vilar
authors.affiliation: Inserm, U1016, Institut Cochin, 22 Rue Méchain, F-75014 Paris, France.|CNRS, UMR8104, 22 Rue Méchain, F-75014 Paris, France.|University of Paris Descartes, Sorbonne Paris Cite, F-75006 Paris, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Mounier
authors.affiliation: Inserm, U1016, Institut Cochin, 22 Rue Méchain, F-75014 Paris, France.|CNRS, UMR8104, 22 Rue Méchain, F-75014 Paris, France.|University of Paris Descartes, Sorbonne Paris Cite, F-75006 Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Chazaud
authors.affiliation: CEA, List institute CEA Saclay, Digitéo Labs, PC192, F-91191 Gif-sur-Yvette, Cedex, France.
authors.forename: Nora
authors.initials: N
authors.lastname: Benhabiles
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, U1135, CNRS, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Boulevard de l'Hôpital, F-75013 Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Boissonnas
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, U1135, CNRS, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Boulevard de l'Hôpital, F-75013 Paris, France.
authors.forename: Béhazine
authors.initials: B
authors.lastname: Combadiere
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Inserm, U1135, CNRS, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Boulevard de l'Hôpital, F-75013 Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Combadiere
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D004546:Elapid Venoms / Q000633:toxicity; D005786:Gene Expression Regulation / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects*; D009135:Muscular Diseases / Q000139:chemically induced* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D004546:Elapid Venoms; D019707:Receptors, Chemokine; C005082:notexin