Ke Fang, Zhang Lingyun, Liu Zhaoyuan, Liu Jinlin, Yan Sha, Xu Zhenyao, Bai Jing, Zhu Huiyuan, Lou Fangzhou, Wang Hong, Shi Yufang, Jiang Yong, Su Bing, Wang Honglin
Shanghai Institute of Immunology, Institute of Medical Sciences, Institute of Health Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Stem Cells. 2014 Oct;32(10):2799-810. doi: 10.1002/stem.1763.
Mesenchymal stem cells (MSCs) have demonstrated promising therapeutic potential for a variety of diseases including autoimmune disorders. A fundamental requirement for MSC-mediated in vivo immunosuppression is their effective trafficking. However the mechanism underlying MSC trafficking remains elusive. Here we report that skin-derived MSCs (S-MSCs) secrete high levels of interleukin-6 (IL-6) in inflammatory conditions. Disruption of the il6 or its signaling transducer gp130 blocks voltage-gated calcium (Ca(2+) ) channels (VGCC) critically required for cell contraction involved in the sequential adhesion and de-adhesion events during S-MSC migration. Deletion of il6 gene leads to a severe defect in S-MSC's trafficking and immunosuppressive function in vivo. Thus, this unexpected requirement of autocrine IL-6 for activating Ca(2+) channels uncovers a previously unrecognized link between the IL-6 signaling and the VGCC and provides novel mechanistic insights for the trafficking and immunomodulatory activities of S-MSCs.
间充质干细胞（MSCs）已显示出对包括自身免疫性疾病在内的多种疾病具有有前景的治疗潜力。MSC介导的体内免疫抑制的一个基本要求是它们的有效运输。然而，MSC运输的潜在机制仍然难以捉摸。在这里，我们报告皮肤来源的间充质干细胞（S-MSCs）在炎症条件下分泌高水平的白细胞介素-6（IL-6）。Il6或其信号转导器gp130的破坏会阻断电压门控钙（Ca(2+)）通道（VGCC），而VGCC是S-MSC迁移过程中顺序粘附和去粘附事件中细胞收缩所必需的。Il6基因的缺失导致S-MSC在体内运输和免疫抑制功能的严重缺陷。因此，自分泌IL-6对激活Ca(2+)通道的这种意外需求揭示了IL-6信号与VGCC之间以前未被认识的联系，并为S-MSCs的运输和免疫调节活性提供了新的机制见解。
