title: Mesenchymal stem/stromal cells induce the generation of novel IL-10-dependent regulatory dendritic cells by SOCS3 activation.
abstract: Suppression of immune response by mesenchymal stem/stromal cells (MSCs) is well documented. However, their regulatory effects on immune cells, especially regulatory dendritic cells, are not fully understood. We have identified a novel Sca-1(+)Lin(-)CD117(-) MSC population isolated from mouse embryonic fibroblasts (MEF) that suppressed lymphocyte proliferation in vitro. Moreover, the Sca-1(+)Lin(-)CD117(-) MEF-MSCs induced hematopoietic stem/progenitor cells to differentiate into novel regulatory dendritic cells (DCs) (Sca-1(+)Lin(-)CD117(-) MEF-MSC-induced DCs) when cocultured in the absence of exogenous cytokines. Small interfering RNA silencing showed that Sca-1(+)Lin(-)CD117(-) MEF-MSCs induced the generation of Sca-1(+)Lin(-)CD117(-) MEF-MSC-induced DCs via IL-10-activated SOCS3, whose expression was regulated by the JAK-STAT pathway. We observed a high degree of H3K4me3 modification mediated by MLL1 and a relatively low degree of H3K27me3 modification regulated by SUZ12 on the promoter of SOCS3 during SOCS3 activation. Importantly, infusion of Sca-1(+)CD117(-)Lin(-) MEF-MSCs suppressed the inflammatory response by increasing DCs with a regulatory phenotype. Thus, our results shed new light on the role of MSCs in modulating regulatory DC production and support the clinical application of MSCs to reduce the inflammatory response in numerous disease states.
authors: 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, Beijing 100005, People's Republic of China.
authors: Xingxia
authors: X
authors: Liu
authors: Xuebin
authors: X
authors: Qu
authors: Yuan
authors: Y
authors: Chen
authors: Lianming
authors: L
authors: Liao
authors: Kai
authors: K
authors: Cheng
authors: Changshun
authors: C
authors: Shao
authors: Martin
authors: M
authors: Zenke
authors: Armand
authors: A
authors: Keating
authors: Robert C H
authors: RC
authors: Zhao
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D053595:Embryonic Stem Cells / Q000276:immunology / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology
chemical_list: C556062:IL10 protein, mouse; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016753:Interleukin-10