title: The effect of immunosuppressive drug cyclosporine A on myeloid-derived suppressor cells in transplanted mice.
abstract: OBJECTIVE
  Myeloid-derived suppressor cells (MDSCs) play important roles in preventing graft rejection. Immunosuppressive drug cyclosporine A (CsA) is widely used in clinics to treat patients with allografts and autoimmune diseases. However, the effect of CsA on CD11b(+)Gr1(+) MDSCs has not been studied.
  
  
  METHODS
  The subjects of the study include BALB/c skin-grafted C57BL/6 mice and the in vitro MDSCs induction system.
  
  
  METHODS
  Skin-grafted mice were treated with CsA (30 mg/kg, i.p.) or control buffer daily. 0.01 μg/ml CsA was added during MDSC induction.
  
  
  METHODS
  Flow cytometry was used to check cell phenotypes and proliferation. Real-time PCR was used for gene expressions. Inducible nitric oxide synthase iNOS-knockout mice were used for the role of iNOS in the immunosuppression of MDSCs.
  
  
  RESULTS
  CsA in MDSC-induction system significantly increased the number of CD11b(+)Gr1(+)MDSCs without detectable effects on the expressions of CD31, CD115 and CD274. However, GM-CSF + CsA-induced MDSCs express higher iNOS than control MDSCs. Blocking iNOS activity by inhibitor or gene deletion significantly reversed the inhibitory effects of GM-CSF + CsA-induced MDSCs on T cell proliferation. Importantly, CsA treatment significantly increased the number and the immunosuppressive ability of CD11b(+)Gr1(+)MDSCs in allogeneic skin-grafted mice.
  
  
  CONCLUSIONS
  CsA promotes MDSC induction and immunosuppressive function, which might be of clinical importance in treating graft rejection and autoimmune diseases.
authors.affiliation: College of Life Science, Henan Normal University, Xinxiang, Henan, China.|Transplantation Biology Research Division, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beichen West Road 1-5, Chaoyang District, 100101, Beijing, China.
authors.forename: Chenlu
authors.initials: C
authors.lastname: Han
authors.affiliation: College of Life Science, Henan Normal University, Xinxiang, Henan, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Kidney Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Na
authors.affiliation: College of Life Science, Henan Normal University, Xinxiang, Henan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Transplantation Biology Research Division, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beichen West Road 1-5, Chaoyang District, 100101, Beijing, China. liwg0618@htu.cn.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Li
authors.affiliation: College of Life Science, Henan Normal University, Xinxiang, Henan, China. zhaoy@ioz.ac.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D016572:Cyclosporine / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072737:Myeloid-Derived Suppressor Cells / Q000187:drug effects* / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D009569:Nitric Oxide; D016572:Cyclosporine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: Graft rejection; Immune tolerance; Innate immunity; Myeloid-derived suppressor cells