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

被引：59

作者：

Arnold, Ludovic ^{[1
]}

Perrin, Helene ^{[1
]}

de Chanville, Camille Baudesson ^{[1
]}

Saclier, Marielle ^{[2
,3
,4
]}

Hermand, Patricia ^{[1
]}

Poupel, Lucie ^{[1
]}

Guyon, Elodie ^{[1
]}

Licata, Fabrice ^{[1
]}

Carpentier, Wassila ^{[5
]}

Vilar, Jose ^{[6
]}

Mounier, Remi ^{[2
,3
,4
]}

Chazaud, Benedicte ^{[2
,3
,4
]}

Benhabiles, Nora ^{[7
]}

Boissonnas, Alexandre ^{[1
]}

Combadiere, Behazine ^{[1
]}

Combadiere, Christophe ^{[1
]}

机构：

[1] Univ Paris 06, Sorbonne Univ, Ctr Immunol & Malad Infect CIMI Paris, Inserm,U1135,CNRS,ERL 8255, F-75013 Paris, France

[2] Inst Cochin Genet Mol, INSERM, U1016, F-75014 Paris, France

[3] CNRS, UMR8104, F-75014 Paris, France

[4] Univ Paris 05, Sorbonne Paris Cite, F-75006 Paris, France

[5] Univ Paris 06, Sorbonne Univ, Plateforme Post Genom Pitie Salpetrie P3S, UMS2 Omique,INSERM US029, F-75013 Paris, France

[6] Paris Ctr Rech Cardiovasc PARCC HEGP, F-75015 Paris, France

[7] CEA Saclay, List Inst, CEA, Digiteo Labs, F-91191 Gif Sur Yvette, France

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

ATHEROSCLEROTIC LESION FORMATION; SKELETAL-MUSCLE; ALTERED INFLAMMATION; FRACTALKINE RECEPTOR; CELL RECRUITMENT; MONOCYTE SUBSETS; CCR2-/-MICE; IN-VIVO; EXPRESSION; ACCUMULATION;

D O I：

10.1038/ncomms9972

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：12

共 57 条

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