title: Autocrine interleukin-6 drives skin-derived mesenchymal stem cell trafficking via regulating voltage-gated Ca(2+) channels.
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 (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.
authors.affiliation: 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.
authors.forename: Fang
authors.initials: F
authors.lastname: Ke
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhaoyuan
authors.initials: Z
authors.lastname: Liu
authors.forename: Jinlin
authors.initials: J
authors.lastname: Liu
authors.forename: Sha
authors.initials: S
authors.lastname: Yan
authors.forename: Zhenyao
authors.initials: Z
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zhu
authors.forename: Fangzhou
authors.initials: F
authors.lastname: Lou
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.forename: Bing
authors.initials: B
authors.lastname: Su
authors.forename: Honglin
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D015220:Calcium Channels / Q000378:metabolism*; D002465:Cell Movement; D002469:Cell Separation; D020405:Dermis / Q000166:cytology; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D012867:Skin / Q000166:cytology*
chemical_list: D015220:Calcium Channels; D015850:Interleukin-6
keywords: Calcium flux; Experimental models; Immunosuppression; Mesenchymal stem cells; Stem cell transplantation; T cells; gp130; siRNA