Zhang Jing, Xiao Zhicheng, Qu Chao, Cui Wei, Wang Xiaonan, Du Jie
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.
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
J Immunol. 2014 Nov 15;193(10):5149-60. doi: 10.4049/jimmunol.1303486. Epub 2014 Oct 22.
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.
炎症微环境在骨骼肌再生中起关键作用。已有报道CD8 T细胞浸润至受损肌肉中。然而，CD8 T细胞在骨骼肌再生过程中的作用仍不清楚。在本研究中，我们使用心脏毒素诱导的小鼠骨骼肌损伤/再生模型来研究CD8 T细胞的作用。与野生型（WT）小鼠相比，CD8α缺陷小鼠的肌肉再生受损且基质沉积增加，野生型小鼠在注射心脏毒素后CD8 T细胞浸润至受损肌肉中。将CD8 T细胞过继转移至CD8α缺陷小鼠可改善肌肉再生并抑制基质重塑。与WT小鼠相比，CD8α缺陷限制了Gr1（高）巨噬细胞（MPs）募集至肌肉中，导致卫星细胞数量减少。与WT小鼠相比，CD8α缺陷小鼠中调节Gr1（高） MPs迁移的MCP-1（MCP-1/CCL2）表达降低。将CD8 T细胞与MPs共培养可促进MCP-1分泌。肌肉内注射MCP-1可显著促进Gr1（高） MPs的募集并改善CD8α缺陷小鼠的肌肉再生。我们得出结论，CD8 T细胞通过调节MCP-1的分泌以募集Gr1（高） MPs参与骨骼肌再生，而Gr1（高） MPs可促进成肌细胞增殖。
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