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Gene expression profiling for 2 cell samples

ABSTRACT: Mesenchymal stem cells (MSCs) exhibit immunosuppressive properties. However the homing mechanisms underlying MSC trafficking to target tissues remain elusive. Here we report that skin-derived MSCs (S-MSCs) secrete high levels of interleukin-6 (IL-6), inhibit T helper (Th)1- and Th17-cell differentiation, and possess IL-6-dependent immunomodulatory capacity in inflammatory microenvironment. Disruption of the il6 locus or its signaling transducer gp130 blocks voltage-operated calcium (Ca2+) channels (VOCC) critically required for cell contraction involved in the sequential adhesion and de-adhesion events during S-MSC migration. IL-6 directly regulates CaV2.3 encoded by cacna1e of R-type Ca2+ channels through the JAK3/STAT3 signaling pathway. Deletion of il6 or silencing CaV2.3 gene expression leads to a severe defect in S-MSC’s homing and immunosuppressive function in vivo. Thus, this unexpected requirement of autocrine IL-6 for activating CaV2.3 Ca2+ channels uncovers a previously unrecognized link between IL-6 signaling and the VOCC, and provides novel mechanistic insights for the immunomodulatory activities of S-MSCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE42914 | GEO | 2012/12/15

SECONDARY ACCESSION(S): PRJNA183879

REPOSITORIES: GEO

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Gene expression profiling for 2 cell samples

Project description:Mesenchymal stem cells (MSCs) exhibit immunosuppressive properties. However the homing mechanisms underlying MSC trafficking to target tissues remain elusive. Here we report that skin-derived MSCs (S-MSCs) secrete high levels of interleukin-6 (IL-6), inhibit T helper (Th)1- and Th17-cell differentiation, and possess IL-6-dependent immunomodulatory capacity in inflammatory microenvironment. Disruption of the il6 locus or its signaling transducer gp130 blocks voltage-operated calcium (Ca2+) channels (VOCC) critically required for cell contraction involved in the sequential adhesion and de-adhesion events during S-MSC migration. IL-6 directly regulates CaV2.3 encoded by cacna1e of R-type Ca2+ channels through the JAK3/STAT3 signaling pathway. Deletion of il6 or silencing CaV2.3 gene expression leads to a severe defect in S-MSC’s homing and immunosuppressive function in vivo. Thus, this unexpected requirement of autocrine IL-6 for activating CaV2.3 Ca2+ channels uncovers a previously unrecognized link between IL-6 signaling and the VOCC, and provides novel mechanistic insights for the immunomodulatory activities of S-MSCs. A two chip study using total RNA recovered from three mixed S-MSCs derived from WT mice and three mixed S-MSCs derived from IL6KO mice.

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