IL-23/IL-17炎症轴在咪喹莫特诱导的小鼠银屑病样皮肤损害中的作用

 目的：观察IL-23/IL-17炎症轴在咪喹莫特诱导的小鼠银屑病样皮损形成过程中的作用及变化规律。方法：雌性BALB/c小鼠随机分为正常对照组和咪喹莫特组，采用PASI评分观察银屑病样小鼠模型皮损动态变化；光镜观察皮损组织形态学变化；细胞因子抗体芯片技术对比检测两组小鼠血清及皮损组织中细胞因子谱的变化；采用流式细胞小球微阵列术、实时荧光定量PCR和蛋白免疫印迹分析技术对小鼠血清及皮肤组织中细胞因子含量、mRNA和蛋白表达水平进行检测；流式细胞术分析外周血及脾细胞成分。结果：咪喹莫特诱导小鼠产生红斑、鳞屑、增厚等典型的银屑病样皮损，并随着给药时间的延长呈现一个抛物线型的动态变化；经咪喹莫特外用刺激后，小鼠皮肤及血清中IL-23/IL-17轴相关细胞因子、Th1、Th2和Treg类细胞因子含量及表达水平均显著升高。IL-23/IL-17轴细胞因子表达也呈现一个先升高后降低的动态变化过程。咪喹莫特组小鼠外周血及脾细胞中树突状细胞比例显著升高，脾细胞中Th17细胞比例升高，约为正常对照组的3～4倍，Treg细胞比例约为正常对照组的2倍。结论：咪喹莫特诱导小鼠产生的皮损症状、病理学特征及细胞因子改变都与银屑病相似，是进行银屑病研究可行的动物模型，该模型制备后第1～8天可模拟疾病的发展阶段。Th17细胞活化及IL-23/IL-17轴参与了该模型皮损的形成，并呈现一个先升高后降低的动态变化过程。Th1细胞介导的炎症反应也参与了该模型皮损的形成，并且伴随Treg 和Th2类细胞因子的反馈性升高。

Role of IL-23/IL-17 inflammatory axis in the pathogenesis of psoriasis-like lesions induced by imiquimod in mice

AIM: To observe the dynamic changes of IL-23/IL-17 inflammatory axis in psoriasis-like lesions of mice induced by imiquimod (IMQ).METHODS: BALB/c female mice were randomly divided into control group and IMQ group. The morphological changes of lesional skin in mice were evaluated according to the psoriasis area and severity index (PASI) and HE staining. cytokine antibody chips were used to determine the cytokine changes in serum and lesions. The mRNA and protein expression of cytokines were analyzed by cytometric bead array, real-time PCR and Western blotting. Moreover, the changes of cellular constituents in the peripheral blood and splenic cells of mice were detected by flow cytometry.RESULTS: Typical psoriasis-like skin lesions, such as red scaly skin plaques, caused by topical IMQ showed a parabolic dynamic change. There was a dynamic increase in proinflammatory cytokines of the IL-23/IL-17 axis in IMQ-treated skin. IMQ application resulted in elevated expression of cytokines related with IL-23/IL-17 inflammatory axis，Th1-type cytokines，Th2-type cytokines and Treg-type cytokines at day 4. IMQ-treated BALB/c mice showed an increased pericentage of dentric cells in peripheral blood and spleen compared with control animals. Percentages of Th17 and Treg in IMQ-treated mice were increased by 3~4 times and twice as compared with control mice, respectively.CONCLUSION: The skin lesions, histopathological features and cytokine changes in mice induced by IMQ are similar to human psoriasis, which are suitable for investigating the pathogenesis of psoriasis as a psoriasis-like model. IL-23/IL-17 axis is involved in the formation of psoriasis-like skin lesions in mice induced by IMQ and presents a dynamic change. Besides, Th1 cell-mediated inflammatory response is also activated in the formation of lesional skin, accompanied by the increase expression of Th2 and Treg cytokines in a feedback mechanism.