title: Mesenchymal stem cells inhibit Th17 cells differentiation via IFN-γ-mediated SOCS3 activation.
abstract: Mesenchymal stem cells (MSCs) are immunoregulatory, and the administration of them has been shown to ameliorate inflammation caused by Th17 cells. However, the mechanisms that contribute to MSC regulation on Th17 cell development are unclear. Here, we found that MSCs could inhibit Th17 cell differentiation through the activation of suppressors of cytokine signaling 3 (SOCS3) when coculture of MSCs and CD4(+)CD25(low)CD44(low)CD62L(high) T cells. Further analysis demonstrated that the inhibitory action was mediated via interferon gamma (IFN-γ), which activated signal transducer and activator of transcription-1 (STAT1) to enhance the expression of SOCS3, leading to STAT3 inhibition. Moreover, stable and reciprocal changes in H3K4me3 and H3K27me3 at the promoters of STAT1, STAT3 and RORγt determined the fate of Th17 cells. These results demonstrate that MSCs may inhibit Th17 differentiation via IFN-γ that activates SOCS3 leading to immunomodulatory effects, suggesting a possible mechanism by which MSCs could act as a cellular approach to attenuate the clinical and pathological manifestations of some autoimmune diseases.
authors.affiliation: Institute of Basic Medical Sciences and School of Basic Medicine, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dongdansantiao, Beijing, 100005, People's Republic of China.
authors.forename: Xingxia
authors.initials: X
authors.lastname: Liu
authors.forename: Shaoda
authors.initials: S
authors.lastname: Ren
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qu
authors.forename: Chaozhuo
authors.initials: C
authors.lastname: Ge
authors.forename: Kai
authors.initials: K
authors.lastname: Cheng
authors.forename: Robert Chun Hua
authors.initials: RC
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D019175:DNA Methylation; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D056747:Immunomodulation; D007371:Interferon-gamma / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D006657:Histones; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma