CD147参与MDSCs免疫表型分类及功能在银屑病发病中的作用及机制研究

MDSCs是骨髓来源的异质性细胞,近年被确定为银屑病新的免疫调控靶点,其免疫表型分子及上游调控尚未完全明确。本课题基于CD147作为银屑病治疗靶点的前期研究基础,发现CD147可作为膜标记分子参与调控MDSCs的数量。本项目拟在临床病例和动物模型中进一步研究CD147在MDSCs的表达情况,明确CD147作为MDSCs表型标记分子的有效性,通过检测功能分子(iNOS,Arginase-1,NO,ROS)和分泌蛋白(IL-10,TGFβ,sCD147)的表达,检测MDSCs对效应T细胞的负调控及其向中性粒细胞转化能力,对比分析G-、M-、CD147+和CD147-MDSC的功能,通过干扰CD147的表达,分析CD147介导MDSCs功能的信号途径。本研究有望探寻出导致银屑病病理三大典型表现(T细胞亚群紊乱、中性粒细胞异常趋化和角质形成细胞过度增殖)的新的通路和靶分子。

Myeloid-derived suppressor cells (MDSCs) is heterogeneous, immature myeloid cells with the ability to suppress the innate and adaptive immune responses. It has identified as novel target cells for immune regulation of psoriasis. However, the upstream regulatory mechanisms of MDSCs in psoriasis have unknown yet. Based on our previous researches, CD147 might be a new therapeutic target for psoriasis. Importantly, we confined that CD147 involved in MDSCs regulation as a potential membrane biomarker. In the current study, we plan to detect the expression of CD147 in MDSCs derived from clinical cases and animal models and assure the effectiveness of CD147. Meanwhile, we also measure the expression of functional molecules (iNOS, Arginase-1, NO, ROS) and secretory proteins (IL-10, TGFβ, sCD147). We will also investigate that MDSCs negative regulate the effector T cells and transform the effector T cells into neutrophil granulocyte. In addition, we will compare with the different types of MDSCs including G-, M-, CD147+, CD147-MDSCs to identify functional differences, and we will explore the potential signaling pathway via CD147 mediation in MDSCs. We want to discover the new signal pathway and target molecule and explain the pathological features of psoriasis including T cell subtype disorder, neutrophil granulocyte abnormal chemotaxis, and excessive keratinocyte proliferation.