Perp在类风湿性关节炎外周Th17细胞存活中的作用研究

项目名称： Perp在类风湿性关节炎外周Th17细胞存活中的作用研究

项目编号： No.81202363

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学免疫学、法医学

项目作者： 王衍堂

作者单位： 成都医学院

项目金额： 23万元

中文摘要： Th17细胞在类风湿性关节炎（RA）的发病中发挥重要作用，其分泌的IL-17等细胞因子直接参与滑膜炎性改变、关节软骨以及骨的破坏。RA病人外周循环Th17细胞明显增加且存活异常，但原因不明。我们通过前期基因芯片筛选发现大鼠胶原诱导关节炎（CIA）模型中Perp表达降低，并进一步在RA病人PBMCs中证实Perp表达也明显降低，且Perp的异常表达还与IL-17以及疾病活动度评分等呈显著负相关。Perp是tetraspan膜蛋白家族成员，近期研究发现Perp与T淋巴细胞存活以及细胞因子分泌密切相关。由此推测，Perp很可能通过调控外周Th17细胞存活影响RA发病。我们将利用CD4-Cre Perp条件敲除鼠建立小鼠关节炎模型，从患者、动物、细胞及分子水平深入研究Perp调控外周Th17细胞存活影响RA发病的作用及机制，为RA的基础研究和免疫治疗提供新的理论依据和实验基础。

中文关键词： 类风湿性关节炎；Perp；Th17细胞；分化；凋亡

英文摘要： T helper type 17 cells (Th17) play a critical role in the pathogenesis of rheumatoid arthritis (RA), their secretion of IL-17A, IL-17F and IL-6 have been identified as important factors in articular cartilage and bone destruction via RANK-RANKL-OPG system. Peripheral Th17 cells from RA patients are significantly increased and abnormal survival, but the reason for its occurrence is unknown. Our preliminary gene chip screening found the reduced expression of Perp in collagen induced arthritis (CIA) rat model, and we validated in RA patients, Perp expression was also significantly lower in PBMCs of patients, and the Perp abnormal expression levels were significantly negative correlated with IL-17 mRNA and disease activity. Perp encoded by the PERP gene, belongs to the tetraspan membrane proteins, and is widely expressed in immune tissues and organs. Recent studies have shown the regulation function of Perp in lymphocyte survival and secretion of inflammatory cytokines. Taking together, we speculate that Perp might be involved in pathogenesis of RA through regulation of circulating Th17 cells survival. We will isolate peripheral CD4+ T cells of RA patients, and ensure that the abnormal Perp expression are related to apoptosis resistance of Th17 cells under the death signal stimulation; and establish the collagen-ind

英文关键词： rheumatoid arthritis；Perp；Th17 cells；differentiation；apoptosis