FOXP3+ T Cells Recruited to Sites of Sterile Skeletal Muscle Injury Regulate the Fate of Satellite Cells and Guide Effective Tissue Regeneration.
FOXP3+ T Cells Recruited to Sites of Sterile Skeletal Muscle Injury Regulate the Fate of Satellite Cells and Guide Effective Tissue Regeneration.
复制标题
DOI：
10.1371/journal.pone.0128094
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Rovere-Querini P
中科院分区：
文献类型：
--
作者：
Castiglioni A;Corna G;Rigamonti E;Basso V;Vezzoli M;Monno A;Almada AE;Mondino A;Wagers AJ;Manfredi AA;Rovere-Querini P
肌肉损伤诱导经典的炎症反应，其中先天免疫系统的细胞迅速侵入组织。巨噬细胞主要参与这种反应，并需要适当的愈合，因为它们是已知的清除细胞碎片和支持卫星细胞分化的重要。在这里，我们试图评估适应性免疫系统在急性损伤后肌肉再生中的作用。我们发现T淋巴细胞在损伤后被瞬时招募到肌肉中，并对肌肉修复产生促肌生成作用。与WT对照相比，我们观察到Rag 2-/- γ-链-/-小鼠损伤后再生肌纤维的横截面积减少，表明T细胞募集促进肌肉再生。骨骼肌浸润性T淋巴细胞以CD 4 + CD 25 + FOXP 3+细胞为主。肌卫星细胞直接暴露于体外诱导的Treg细胞有效地增强了它们的扩增，同时抑制了它们的肌源性分化。在体内，急性损伤的肌肉的募集限制在卫星扩张的时间段内，可能对炎性疾病持续存在的情况有重要影响，如肌营养不良和炎性肌病。我们的结论是，适应性免疫系统，特别是调节性T细胞，是关键参与有效的骨骼肌再生。因此，除了它们作为免疫/炎症反应的调节剂的公认作用之外，T调节细胞还调节骨骼肌前体细胞的活性，并且有助于该组织的适当再生。
Muscle injury induces a classical inflammatory response in which cells of the innate immune system rapidly invade the tissue. Macrophages are prominently involved in this response and required for proper healing, as they are known to be important for clearing cellular debris and supporting satellite cell differentiation. Here, we sought to assess the role of the adaptive immune system in muscle regeneration after acute damage. We show that T lymphocytes are transiently recruited into the muscle after damage and appear to exert a pro-myogenic effect on muscle repair. We observed a decrease in the cross-sectional area of regenerating myofibers after injury in Rag2-/- γ-chain-/- mice, as compared to WT controls, suggesting that T cell recruitment promotes muscle regeneration. Skeletal muscle infiltrating T lymphocytes were enriched in CD4+CD25+FOXP3+ cells. Direct exposure of muscle satellite cells to in vitro induced Treg cells effectively enhanced their expansion, and concurrently inhibited their myogenic differentiation. In vivo, the recruitment of Tregs to acutely injured muscle was limited to the time period of satellite expansion, with possibly important implications for situations in which inflammatory conditions persist, such as muscular dystrophies and inflammatory myopathies. We conclude that the adaptive immune system, in particular T regulatory cells, is critically involved in effective skeletal muscle regeneration. Thus, in addition to their well-established role as regulators of the immune/inflammatory response, T regulatory cells also regulate the activity of skeletal muscle precursor cells, and are instrumental for the proper regeneration of this tissue.
登录
查看更多内容
影响因子：
4.6
作者：
Kharraz Y;Guerra J;Mann CJ;Serrano AL;Muñoz-Cánoves P
通讯作者：
Muñoz-Cánoves P
影响因子：
3.9
作者：
Jewett A;Man YG;Tseng HC
通讯作者：
Tseng HC
影响因子：
--
作者：
Al-Shanti, Nasser;Durcan, Peter;Stewart, Claire E.
通讯作者：
Stewart, Claire E.
影响因子：
13.3
作者：
Sciorati, Clara;Monno, Antonella;Rovere-Querini, Patrizia
通讯作者：
Rovere-Querini, Patrizia
影响因子：
8
作者：
通讯作者：
--