BAFF干扰的树突状细胞参与自身免疫性关节炎免疫耐受的作用和机制

项目名称： BAFF干扰的树突状细胞参与自身免疫性关节炎免疫耐受的作用和机制

项目编号： No.31200675

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 免疫学

项目作者： 常艳

作者单位： 安徽医科大学

项目金额： 23万元

中文摘要： 体外构建调节性树突状细胞（DCreg）诱导免疫耐受是自身免疫病免疫功能重建的重要手段。B淋巴细胞活化因子（BAFF）是B、T细胞存活和活化的重要调节因子。树突状细胞（DC）是BAFF的主要产生细胞，BAFF通过自分泌或旁分泌诱导DC的免疫原性从而调节T、B细胞活化，那么体外BAFF基因沉默骨髓源DC能否诱导DCreg？诱导的DCreg能否通过调控调节性T细胞（Treg）介导免疫耐受？DCreg通过怎样的机制调控Treg，重建免疫功能，发挥治疗自身免疫病的作用？本项目在以往研究的基础上，BAFF基因沉默骨髓源DC诱导DCreg，体外观察DCreg对Treg的作用和调控机制；体内鸡Ⅱ型胶原（CCⅡ）诱导的DCreg过继转移胶原性关节炎小鼠，探讨抗原特异性免疫调节的治疗作用和机制。本项目拟构建一个以免疫耐受为理论基础的细胞免疫疗法，为临床治疗类风湿关节炎等自身免疫病提供理论依据和技术平台。

中文关键词： 类风湿关节炎；免疫耐受；T细胞；DC；BAFF

英文摘要： Inducing immune tolerance by building regulatory dendritic cells (DCreg) in vitro is an important means of reconstitution immune function in autoimmune diseases. The B lymphocyte-activating factor (BAFF) plays an important roles in regulating B and T cell survival and activation. BAFF is mainly produced by DC. BAFF regulates T and B cell activation may through induction of DC immunity in an autocrine or paracrine manner. Whether or not BAFF gene silencing bone marrow-derived DC induce Dcreg? Whether or not induced DCreg mediates immune tolerance through regulating regulatory T cells (Treg)? How the Dcreg regulate Treg, rebuilding immune function, exerting treatment roles in autoimmune disease? Base on previous studies, in vitro we observe the roles and mechanisms of DCreg on Treg through BAFF gene silencing bone marrow-derived DC to induce Dcreg. In vivo, we investigate the effects and the mechanisms of DCreg induced by CCII on collagen-induced arthritis (CIA) rats. The project intends to build a cell immunotherapy based on the theory of immune tolerance, which may provide theoretical basis and technology platform for the treatment of autoimmune diseases.

英文关键词： rheumatoid arthritis；immune tolerance；T cell；DC；BAFF