title: CD8 T cells are involved in skeletal muscle regeneration through facilitating MCP-1 secretion and Gr1(high) macrophage infiltration.
abstract: Inflammatory microenvironments play a key role in skeletal muscle regeneration. The infiltration of CD8 T cells into injured muscle has been reported. However, the role of CD8 T cells during skeletal muscle regeneration remains unclear. In this study, we used cardiotoxin-induced mouse skeletal muscle injury/regeneration model to investigate the role of CD8 T cells. Muscle regeneration was impaired and matrix deposit was increased in CD8α-deficient mice compared with wild-type (WT) mice whose CD8 T cells were infiltrated into damaged muscle after cardiotoxin injection. Adoptive transfer of CD8 T cells to CD8α-deficient mice improved muscle regeneration and inhibited matrix remodeling. Compared with WT mice, CD8α deficiency limited the recruitment of Gr1(high) macrophages (MPs) into muscle, resulting in the reduction of satellite cell number. The expression of MCP-1 (MCP-1/CCL2), which regulates the migration of Gr1(high) MPs, was reduced in CD8α-deficient mice compared with WT mice. Coculture CD8 T cells with MPs promoted MCP-1 secretion. The i.m. injection of MCP-1 markedly promoted the recruitment of Gr1(high) MPs and improved muscle regeneration in CD8α-deficient mice. We conclude that CD8 T cells are involved in skeletal muscle regeneration by regulating the secretion of MCP-1 to recruit Gr1(high) MPs, which facilitate myoblast proliferation.
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing 100029, China; and Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing 100029, China; and Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing 100029, China; and Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Qu
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing 100029, China; and Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing 100029, China; and Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing 100029, China; and Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China jdu@bcm.edu.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054715:Cardiotoxins / Q000494:pharmacology; D002465:Cell Movement; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects / Q000276:immunology* / Q000293:injuries / Q000473:pathology; D032446:Myoblasts / Q000166:cytology / Q000502:physiology; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D012038:Regeneration; D015398:Signal Transduction
chemical_list: D016827:CD8 Antigens; C431698:CD8alpha antigen; D054715:Cardiotoxins; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine