title: CD14+ monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells.
abstract: Here, the effect of CD14(+) monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-gamma (IFN-gamma) secretion capacities of CD4(+) and CD8(+) T cells in response to anti-CD3/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of prostaglandin synthesis inhibitors (indomethacin or NS-398) almost completely abrogated the immunosuppression activity of hUC-MSCs, identifying prostaglandin E(2) (PGE(2)) as an important soluble mediator. CD14(+) monocytes were found to be able to enhance significantly the immunosuppressive effect of hUC-MSCs in a dose-dependent fashion. Moreover, the inflammatory cytokine IL-1beta, either exogenously added or produced by CD14(+) monocytes in culture, could trigger expression of high levels of PGE(2) by hUC-MSCs, whereas inclusion of the IL-1 receptor antagonist (IL-1RA) in the culture down-regulated not only PGE(2) expression, but also reversed the promotional effect of CD14(+) monocytes and partially restored CD4(+) and CD8(+) T cell proliferation and IFN-gamma secretion. Our data demonstrate an important role of monocytes in the hUC-MSC-induced immunomodulation, which may have important implications in future efforts to explore the clinical potentials of hUC-MSCs.
authors.affiliation: The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, 288 Nanjing Road, Tianjin 300020, China. qqhewd@gmail.com
authors.forename: Ding
authors.initials: D
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.forename: Wei Ting
authors.initials: WT
authors.lastname: Du
authors.forename: Zhi-Bo
authors.initials: ZB
authors.lastname: Han
authors.forename: He
authors.initials: H
authors.lastname: Ren
authors.forename: Ying
authors.initials: Y
authors.lastname: Chi
authors.forename: Shao Guang
authors.initials: SG
authors.lastname: Yang
authors.forename: Francis
authors.initials: F
authors.lastname: Bayard
authors.forename: Delin
authors.initials: D
authors.lastname: Zhu
authors.forename: Zhong Chao
authors.initials: ZC
authors.lastname: Han
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000502:physiology*; D007155:Immunologic Factors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D018836:Inflammation Mediators / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D012995:Solubility; D014470:Umbilical Cord / Q000166:cytology / Q000276:immunology*
chemical_list: D007155:Immunologic Factors; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D008934:Mitogens; D015232:Dinoprostone