狼疮性肾炎足细胞的天然免疫调节作用研究

项目名称： 狼疮性肾炎足细胞的天然免疫调节作用研究

项目编号： No.81200508

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 蔡敏超

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 狼疮性肾炎（LN）主要以肾脏免疫复合物沉积及炎症细胞浸润为主要特点，其发病机制尚不清楚。我们发现，LN足细胞可表达属树突状细胞（DC）标志的天然免疫分子DC-SIGN，并具备专职抗原递呈细胞功能，推测可能依赖其糖识别特性与LN免疫复合物主要抗体IgG所含糖基化修饰GlcNAc结合，在LN足细胞及肾小球损伤中发挥关键作用。本研究拟结合体内外实验，观察LN足细胞DC-SIGN细胞黏附，刺激T细胞增殖与分化，及LSP-1、Raf-1、PI3K、ERK、NF-κB等相关信号通路。进一步采用前沿亲和色谱法及Western Blot法检测足细胞DC-SIGN与LN免疫复合物中IgG及其所含GlcNAc结合识别。系统探讨足细胞及其DC-SIGN调控在LN免疫应答及肾小球损伤中的作用机制。籍此，以DC-SIGN为靶点，为阐明足细胞免疫调控与LN肾小球损伤关系提供新的理论依据，为临床防治寻找新的干预途径。

中文关键词： 狼疮性肾炎；足细胞；DC-SIGN；免疫调节；肾小球损伤

英文摘要： Lupus nephritis (LN) is characterized by the deposit of immune complex and the infiltration of inflammatory cells in kidney. However its pathogenesis remains unclear. We found that the podocytes in LN expressed DC-SIGN, an innate immune molecule predominantly expressed on dendritic cells (DCs). Furthermore, DC-SIGN on podocytes in LN also functioned as a professional antigen presenting cell. Therefore we speculate that, dependent on its property of carbohydrate recognition, DC-SIGN may interact with GlcNAc in IgG, the main antibody in LN immune complex, and play a critical role in the injury of podocytes and glomeruli in LN. The present study plans to observe the cell adhesion, induction of T cell proliferation and differentiation, signaling pathway including LSP-1, Raf-1, PI3K, ERK and NF-κB of DC-SIGN expressed on podocytes in LN. Then frontal affinity chromatograpthy and Western Blot will be used to detect the combination between DC-SIGN and GlcNAc in IgG in LN. Therefore the regulation of podocytes and its DC-SIGN in LN immune response and glomerular injury will be systematically explored. We hope that it will provide new theoretical evidence for the relation between podocyte immune regulation and glomerular injury in LN, and search for a new interference pathway for clinical treatment and prevention.

英文关键词： lupus nephritis；podocyte；DC-SIGN；immunoregulation；glomerular injury