小柯机器人

德国环境卫生研究中心Carolin Daniel课题组发现，调节性T细胞需要IL6受体alpha信号来控制骨骼肌功能和再生。该项研究成果于2023年9月20日在线发表在《细胞—代谢》杂志上。

研究人员发现运动能稳定地诱导高功能的肌肉驻留性节性 T 细胞（Treg），并增加双调节蛋白（Areg）、表皮生长因子受体（EGFR）和ST2的表达。从机理上讲，研究人员发现在T细胞上缺乏IL6Rα的小鼠（TKO）的肌肉Treg功能以及卫星细胞和纤维脂肪生成祖细胞显著减少，而这些细胞是肌肉再生所需的。利用运动和肌肉疏松症模型，IL6Rα TKO小鼠显示出Treg的缺陷、其功能成熟以及肌肉质量更明显的下降。肌肉损伤模型表明，IL6Rα TKO小鼠在肌肉再生方面有明显缺陷。Treg功能的获得可恢复IL6Rα TKO小鼠受损的肌肉修复功能。值得注意的是，在WT小鼠中进行IL6R药理阻断可表征在IL6Rα TKO小鼠中发现的肌肉功能缺陷，从而突出了这些发现的临床意义。

据介绍，驻留在肌肉中的Treg控制着局部组织的完整性和功能。然而，连接基于Treg的调节与肌肉功能和再生的分子界面在很大程度上仍未被探索。

附：英文原文

Title: Regulatory T cells require IL6 receptor alpha signaling to control skeletal muscle function and regeneration

Author: Maike Becker, Sini S. Joseph, Francisco Garcia-Carrizo, Robby Z. Tom, Daria Opaleva, Isabelle Serr, Matthias H. Tschp, Tim J. Schulz, Susanna M. Hofmann, Carolin Daniel

Issue&Volume: 2023-09-20

Abstract: Muscle-residing regulatory T cells (Tregs) control local tissue integrity and function. However, the molecular interface connecting Treg-based regulation with muscle function and regeneration remains largely unexplored. Here, we show that exercise fosters a stable induction of highly functional muscle-residing Tregs with increased expression of amphiregulin (Areg), EGFR, and ST2. Mechanistically, we find that mice lacking IL6Rα on T cells (TKO) harbor significant reductions in muscle Treg functionality and satellite and fibro-adipogenic progenitor cells, which are required for muscle regeneration. Using exercise and sarcopenia models, IL6Rα TKO mice demonstrate deficits in Tregs, their functional maturation, and a more pronounced decline in muscle mass. Muscle injury models indicate that IL6Rα TKO mice have significant disabilities in muscle regeneration. Treg gain of function restores impaired muscle repair in IL6Rα TKO mice. Of note, pharmacological IL6R blockade in WT mice phenocopies deficits in muscle function identified in IL6Rα TKO mice, thereby highlighting the clinical implications of the findings.

DOI: 10.1016/j.cmet.2023.08.010

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00331-5

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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