title: Umbilical Cord-derived Mesenchymal Stem Cells Instruct Monocytes Towards an IL10-producing Phenotype by Secreting IL6 and HGF.
abstract: Human UC-MSCs are regarded as an attractive alternative to BM-MSCs for clinical applications due to their easy preparation, higher proliferation and lower immunogenicity. However, the mechanisms underlying immune suppression by UC-MSCs are still unclear. We studied the mechanism of inhibition by UC-MSCs during the differentiation of monocytes into DCs and focused on the specific source and the role of the involved cytokines. We found that UC-MSCs suppressed monocyte differentiation into DCs and instructed monocytes towards other cell types, with clear decreases in the expression of co-stimulatory molecules, in the secretion of inflammatory factors and in allostimulatory capacity. IL6, HGF and IL10 might be involved in this process because they were detected at higher levels in a coculture system. UC-MSCs produce IL-6 and HGF, and neutralization of IL-6 and HGF reversed the suppressive effect of UC-MSCs. IL10 was not produced by UC-MSCs but was exclusively produced by monocytes after exposure to UC-MSCs, IL-6 or HGF. In summary, we found that the UC-MSC-mediated inhibitory effect was dependent on IL6 and HGF secreted by UC-MSCs and that this effect induced monocyte-derived cells to produce IL10, which might indirectly strengthen the suppressive effect of UC-MSCs.
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
authors.forename: Yingcai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
authors.forename: Linsen
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.|Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Guihua
authors.initials: G
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.|Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
mesh_terms: D002450:Cell Communication; D002454:Cell Differentiation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D061251:Primary Cell Culture; D015398:Signal Transduction
chemical_list: C066855:HGF protein, human; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016753:Interleukin-10; D017228:Hepatocyte Growth Factor