title: Mesenchymal stem cells overexpressing IL-35 effectively inhibit CD4+T cell function.
abstract: Mesenchymal stem cells (MSCs) have recently emerged as promising candidates for cell-based immune tolerance therapy. Interleukin 35 (IL-35) is a relatively newly identified cytokine required for the regulatory and suppressive functions of regulatory T cells (Treg), playing an important role in the prevention of autoimmune diseases. In this study, we isolated adipose tissue-derived MSCs, a good vehicle for cell therapy, which were transfected with a lentivirus vector for the overexpression of the therapeutic murine IL-35 gene. IL-35 levels in transfected MSCs (IL-35-MSCs) were quantified by ELISA. Co-culture of CD4+T cells and IL-35-MSCs resulted in the inhibition of CD4+T cell proliferation and IL-17A secretion. In addition, IL-35-MSCs induced IL-10 production by CD4+T cells, but did not affect IFN-γ. These findings suggested that MSCs over-expressing IL-35 had higher immunosuppressive capacity compared with non-transfected MSCs, and may provide a useful approach for basic research on gene therapy for autoimmune disorders.
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: nasy3367@126.com.
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Hongyue
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Yongjia
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: He
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D007167:Immunotherapy / Q000379:methods*; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D007378:Interleukins; C569375:interleukin-35, mouse; D016753:Interleukin-10
keywords: CD4(+) T cells; Interleukin-35; Lentivirus; Mesenchymal stem cells