T淋巴细胞在抗LEG3抗体介导的系统性红斑狼疮皮肤血管炎发病机制中的作用

项目名称： T淋巴细胞在抗LEG3抗体介导的系统性红斑狼疮皮肤血管炎发病机制中的作用

项目编号： No.81472877

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王亮春

作者单位： 中山大学

项目金额： 90万元

中文摘要： 大约54%的系统性红斑狼疮（SLE）患者有血管炎改变，90%表现为皮肤血管炎。 我们前期研究发现，80%有皮疹的SLE患者抗LEG3抗体阳性，抗体滴度随皮疹好转逐渐下降；纯化血清抗LEG3抗体经皮内注射引起皮肤血管炎，为免疫复合物介导血管炎理论提供了直接证据。任何抗体介导的靶器官免疫性损伤都离不开T细胞的调节。本课题利用我们已经建立的动物模型，深入研究T细胞在抗LEG3抗体介导的皮肤血管炎发生机制中的作用：①LEG3抗体对血管内皮细胞表面分子和分泌细胞因子的影响；② 上述内环境决定炎症组织内T细胞亚群构成；③ T细胞亚群分泌相关细胞因子促进血管炎发生；④改变T细胞亚群；局部皮肤内补充外源性或中和内源性关键细胞因子，可以调节抗LEG3抗体所介导的皮肤血管炎的发生、发展和炎症消褪过程， 为皮肤血管炎的局部治疗提供理论和实验依据。

中文关键词： 系统性红斑狼疮；皮肤血管炎；T细胞；自身抗体

英文摘要： Vasculitis is one of the prominent syndromes in systemic lupus erythematosus patients (SLE), of which , about 90% presents as cutaneous vasculitis. Our previous researches demonstrated that 80% of SLE patients with skin lesions were detected with anti-LEG3 antibodies, which decreased with skin recovery. Affinity purified anti-LEG3 antibodies induced cutaneous vasculitis after intradermal injection into mouse skin. These findings for the first time to provide direct evidences for immune complex mediated vasculitis. T cell is a key regulator in antibody induced tissue damages. In this project, we will investigate the T cell effect on anti-LEG3 antibody mediated cutaneous vasculitis in SLE. Using the animal model, we'll characterize the adhesion molecules and cytokines produced by endothelial cells in the presence of anti-LEG3 antibody by flow cytometry and real-time PCR, evaluate the subsets of T cells infiltrating in the skin lesions by immunohistochemistry, test the pathogenic effect of cytokines produced by the subsets of T cell by histological examination, and determine the effect of these T cells and cytokines on the initiation, development and prognosis of cutaneous vasculitis by adding exogenous or neutralizing the endogensous molecules. With this project, we are hoping to reveal the mechanism of T cells in regulating anti-LEG3 antibody mediated cutaneous vascuilitis, and to provide evidences for developing new topical reagents to manage skin vasculitis.

英文关键词： systemic lupus erythematosus;cutaneous vasculitis;T cell;autoantibody