title: Umbilical cord-derived mesenchymal stem cells instruct dendritic cells to acquire tolerogenic phenotypes through the IL-6-mediated upregulation of SOCS1.
abstract: The mechanisms responsible for the inhibitory effects of mesenchymal stem cells (MSCs) on dendritic cells (DCs) are still poorly understood. Our investigation of the potential signaling pathways revealed for the first time that human umbilical-cord-derived MSCs (UC-MSCs) instruct DCs to acquire tolerogenic phenotypes through the IL-6-mediated upregulation of SOCS1. This subset of MSC-DCs exhibited a tolerogenic pattern, with a clear decrease in the expression of co-stimulatory molecules and the capacity to stimulate CD3(+) T cell proliferation and inflammatory factor secretion, and a significant increase in the production of inhibitory cytokine IL-10 and the ability to induce Treg cells and Th2 responses. Adoption of this tolerogenic pattern required the activation of SOCS1, which blocked DC maturation by impairing TLR4 signaling. The effects of UC-MSCs on SOCS1 activation were essentially mediated by the JAK-STAT pathway via IL-6 secretion. In summary, our data identify a new mechanism, involving the IL-6-mediated upregulation of SOCS1, by which UC-MSCs instruct DCs to acquire tolerogenic phenotypes.
authors.affiliation: 1 Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou, China .
authors.forename: Yinan
authors.initials: Y
authors.lastname: Deng
authors.forename: Shuhong
authors.initials: S
authors.lastname: Yi
authors.forename: Guoying
authors.initials: G
authors.lastname: Wang
authors.forename: Jintao
authors.initials: J
authors.lastname: Cheng
authors.forename: Yingcai
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wenjie
authors.initials: W
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Tai
authors.forename: Shaohong
authors.initials: S
authors.lastname: Chen
authors.forename: Guihua
authors.initials: G
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
mesh_terms: D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007108:Immune Tolerance; D015850:Interleukin-6 / Q000502:physiology*; D053612:Janus Kinases / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D010641:Phenotype; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D015533:Transcriptional Activation; D014470:Umbilical Cord / Q000166:cytology; D015854:Up-Regulation
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; C108944:SOCS1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D053612:Janus Kinases