鼠RPE细胞分泌的mBD-14参与EAU小鼠免疫豁免重建的机制研究

项目名称： 鼠RPE细胞分泌的mBD-14参与EAU小鼠免疫豁免重建的机制研究

项目编号： No.81200675

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： 章淑杰

作者单位： 复旦大学

项目金额： 23万元

中文摘要： 葡萄膜炎是一种严重的自身免疫性眼科疾病。在葡萄膜炎发病机制中，视网膜色素上皮细胞（RPE）的免疫豁免机制的破坏扮演了重要角色。因此，进一步阐明RPE免疫豁免功能在葡萄膜炎中的作用对于寻找新的治疗方案是迫切需要的。我们推测：RPE表达的人beta-防御素-3（HBD-3）具有广谱杀菌能力和诱导免疫豁免的双重作用，HBD-3可通过重建免疫豁免微环境抑制眼内自身免疫炎症。mBD-14是HBD-3在小鼠内的同源分子。我们将在基因和蛋白水平分析HBD-3/mBD-14在视网膜色素上皮的时空表达模式，研究HBD-3/mBD-14通过对Treg细胞的诱导发挥对特异性免疫反应的抑制作用，并在小鼠EAU模型中通过外源性加入mBD-14重建眼免疫豁免微环境，评价其对葡萄膜炎模型的治疗效果。该研究将从新的角度阐释了眼免疫豁免机制，为自身免疫性葡萄膜炎的治疗寻找到重要突破口。

中文关键词： 视网膜色素上皮细胞；免疫豁免；炎症小体；IL-17A；

英文摘要： Uveitis is a clinically common heterogenous group of diseases in which intraocular inflammation leads to reduced vision, retinal destruction, and blindness. Because its cause and pathogenesis are very complicated, there are still no satisfactory therapy methods to cure uveitis. In recent years, with the development of molecular biology and immunology, uveitis were more and more considered as organ-specific antoimmune disease.Studies have shown that, in the pathogenesis of uveitis,the damage of the immune privilege machanisms of retinal pigment epithelium (retinal pigment epithelium, RPE)would play an important role. Therefore, to study the RPE immune privilege function in uveitis is improtant for searching new treatment options.The study of mBD-14 gene expression patterns in PRE cells and in experimental autoimmune uveitis (experimental autoimmune uveitis, EAU)animal models based on our previous work. In our work,the mBD-14 gene will be overexpression or knockdown with lenti-virus infection system to RPE cells,then to study the immune privilege function of the RPE cells. mBD-14 may be a promising therapeutic target endophthalmitis.

英文关键词： retinal pigment epithelium; RPE；immune privilege；inflammasome；IL-17A；