Poor Repair of Skeletal Muscle in Aging Mice Reflects a Defect in Local, Interleukin-33-Dependent Accumulation of Regulatory T Cells.
Poor Repair of Skeletal Muscle in Aging Mice Reflects a Defect in Local, Interleukin-33-Dependent Accumulation of Regulatory T Cells.
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DOI：
10.1016/j.immuni.2016.01.009
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发表时间：
2016-02-16
期刊：
影响因子：
32.4
通讯作者：
Mathis D
中科院分区：
文献类型：
--
作者：
Kuswanto W;Burzyn D;Panduro M;Wang KK;Jang YC;Wagers AJ;Benoist C;Mathis D
骨骼肌的正常修复需要Foxp 3 + CD 4+调节性T（Treg）细胞的特殊群体的局部扩增。这些细胞不能在老年小鼠急性损伤的肌肉中积累，已知老年小鼠的肌肉修复无效。这种缺陷反映了Treg细胞向受损肌肉的募集减少，以及其中较少的增殖和保留。白细胞介素（IL）-33调节年轻小鼠肌肉Treg细胞的稳态，其给药老年小鼠改善其Treg细胞积累和肌肉再生的缺陷。骨骼肌中的主要IL-33表达细胞显示出一系列可诊断成脂/成脂祖细胞的标志物，并且通常与神经结构相关，包括神经纤维、神经束和肌梭，它们是对本体感受重要的拉伸敏感性机械感受器。IL-33+细胞在肌肉损伤后更频繁，并且在老年小鼠中减少。IL-33很好地定位于在肌肉环境中的神经和免疫系统之间传递信号。
Normal repair of skeletal muscle requires local expansion of a special population of Foxp3+CD4+ regulatory T (Treg) cells. Such cells failed to accumulate in acutely injured muscle of old mice, known to undergo ineffectual repair. This defect reflected reduced recruitment of Treg cells to injured muscle, as well as less proliferation and retention therein. Interleukin (IL)-33 regulated muscle Treg cell homeostasis in young mice, and its administration to old mice ameliorated their deficits in Treg cell accumulation and muscle regeneration. The major IL-33-expressing cells in skeletal muscle displayed a constellation of markers diagnostic of fibro/adipogenic progenitor cells, and were often associated with neural structures, including nerve fibers, nerve bundles and muscle spindles, which are stretch-sensitive mechanoreceptors important for proprioception. IL-33+ cells were more frequent after muscle injury, and were reduced in old mice. IL-33 is well situated to relay signals between the nervous and immune systems within the muscle context.