他克莫司通过抑制Th17治疗咪喹莫特诱导的银屑病小鼠模型

Tacrolimus Therapy for Imiquimod-induced Psoriasis-like Mouse Models via Inhibiting Th17 Cells

目的研究他克莫司对银屑病小鼠模型中Th17和相关细胞因子表达的影响。方法以咪喹莫特(imiquimod,IMQ)诱导建立银屑病样的小鼠模型。采用组织病理分析研究银屑病样皮损炎症状况;流式细胞仪分析循环血中T细胞的水平;免疫组化法检测细胞因子水平;Western blot法分析体外分离的T细胞中Jak/Stat3的表达;实时定量RT-PCR检测RORc-t mRNA的表达。结果他克莫司治疗能改善IMQ诱导的角质形成细胞的增殖,减少银屑病皮损处浸润的CD3+T细胞数,减少循环血中CD4^+和CD8^+T细胞数,并降低循环血中炎性细胞因子(IL-17A、TNF-α、IL-6、IFN-γ、IL-10、IL-4和IL-2)水平。此外,他克莫司可抑制Th17细胞分化和体外分离的T细胞分泌IL-17A,抑制Th17细胞中的Jak/Stat3信号通路,上调银屑病皮损处细胞信号抑制因子1(SOCS1)的表达。结论他克莫司对银屑病的治疗作用可能是通过抑制Th17相关炎症,减轻银屑病样皮损实现的。

Objective To examine the effect of tacrolimus（TAC）on Th17 cells and related cytokines in the psoriasis-like mouse model.Methods An imiquimod（IMQ）-induced psoriasis-like mouse model was established.TAC（2mg/kg）was intraperitoneally given every two days for 9 days.The inflammation of psoriasis-like lesions was assessed by pathological analysis,circulating T cells by flow cytometry and cytokines by immunohistochemistry.The expression of Jak/Stat3 and SOCS1 in isolated T cells was detected by Western blotting and RORc-t expression by real-time RT-PCR.Results TAC could suppress the IMQ-induced keratinocyte proliferation and the inltration of CD3^＋cells to psoriatic lesions.It could inhibit the elevations of circulating CD4^＋and CD8^＋T cells and inflammatory cytokines（IL-17 A,TNF-α,IL-6,IFN-γ,IL-10,IL-4and IL-2）.Additionally,TAC could inhibit the Th17 cell differentiation,IL-17 Asecretion by isolated T cells and Jak/Stat3 signaling pathway in Th17 cells,and upregulate the expression of SOCS1 in Th17cells in psoriatic lesions.Conclusion TAC alleviates psoriasis-like skin lesions by inhibiting Th17-related inflammation.