Autocrine Interleukin-6 Drives Skin-Derived Mesenchymal Stem Cell Trafficking via Regulating Voltage-Gated Ca2+ Channels

Authors

  • Fang Ke,

    1. 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
    Search for more papers by this author
  • Lingyun Zhang,

    1. 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
    Search for more papers by this author
  • Zhaoyuan Liu,

    1. 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
    Search for more papers by this author
  • Jinlin Liu,

    1. 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
    Search for more papers by this author
  • Sha Yan,

    1. 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
    Search for more papers by this author
  • Zhenyao Xu,

    1. 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
    Search for more papers by this author
  • Jing Bai,

    1. 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
    Search for more papers by this author
  • Huiyuan Zhu,

    1. 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
    Search for more papers by this author
  • Fangzhou Lou,

    1. 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
    Search for more papers by this author
  • Hong Wang,

    1. 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
    Search for more papers by this author
  • Yufang Shi,

    1. The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    2. Child Health Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA
    Search for more papers by this author
  • Yong Jiang,

    1. Department of Pathophysiology, Southern Medical University, Guangzhou, Guangdong, China
    Search for more papers by this author
  • Bing Su,

    1. 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
    2. Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA
    Search for more papers by this author
  • Honglin Wang

    Corresponding author
    1. 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
    2. Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Institute of Health Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    • Correspondence: Honglin Wang, Ph.D., Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, 200025 Shanghai, China. Telephone: +86-21-63846590, ext. 776654; Fax: +86-21-64660996; e-mail: honglin.wang@sjtu.edu.cn

    Search for more papers by this author

Abstract

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 (Ca2+) 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 Ca2+ 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. Stem Cells 2014;32:2799–2810

Ancillary