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The effect of immunosuppressive drug cyclosporine A on myeloid-derived suppressor cells in transplanted mice.
Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.] 2016 September
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.
SUBJECTS: The subjects of the study include BALB/c skin-grafted C57BL/6 mice and the in vitro MDSCs induction system.
TREATMENT: 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.
SUBJECTS: The subjects of the study include BALB/c skin-grafted C57BL/6 mice and the in vitro MDSCs induction system.
TREATMENT: 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.
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