title: TGF-β promotes immune responses in the presence of mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) possess potent immunosuppression capacity and could exert strong therapeutic effects in many diseases, especially inflammatory disorders, in animal models and clinical settings. Although inflammatory cytokines are critical in inducing the immune modulatory properties of MSCs, detailed molecular mechanisms are yet to be fully understood. TGF-β is a well-known anti-inflammatory cytokine and exists in various inflammatory processes; therefore, we investigated whether it could synergize with MSCs in suppressing immune responses. To our surprise, we found that TGF-β actually reversed the immunosuppressive effect of MSCs on anti-CD3 activated splenocytes. Using TGF-β unresponsive MSCs, we demonstrated that the TGF-β directly acted on MSCs. Furthermore, we showed that the effect of TGF-β is exerted through inhibiting inflammatory cytokines induced inducible NO synthase (iNOS) expression in a SMAD3-dependent manner. Interestingly, we found that TGF-β produced by MSCs could act in an autocrine manner to reduce inflammatory cytokine-induced inducible NO synthase expression by MSCs themselves. Therefore, our study revealed a previously unrecognized property of TGF-β in promoting immune responses in the presence of MSCs.
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
authors.forename: Chunliang
authors.initials: C
authors.lastname: Xu
authors.forename: Pengfei
authors.initials: P
authors.lastname: Yu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Han
authors.forename: Liming
authors.initials: L
authors.lastname: Du
authors.forename: Jianhe
authors.initials: J
authors.lastname: Gan
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D007108:Immune Tolerance / Q000187:drug effects* / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D052247:Nitric Oxide Synthase Type II