Behcet病、Vogt-小柳原田综合征是我国致盲率最高的葡萄膜炎类型，Th1、Th17和Treg细胞数量及功能紊乱是其发病基础。最近研究发现颗粒素蛋白前体（progranulin，PGRN)具有免疫调节作用，我们预实验发现活动期Behcet病和VKH综合征患者PGRN表达显著降低。因此本项目以PGRN为研究切入点，以葡萄膜炎动物模型和视网膜色素上皮细胞为研究对象，通过给予外源性重组PGRN或PGRN基因缺陷正反两方面验证PGRN对葡萄膜炎动物模型发生、发展及转归的影响及对Th17、Th1和Treg细胞分化和功能的影响；探讨PGRN对眼局部视网膜色素上皮细胞的作用及其具体通路。通过上述研究，以期阐明PGRN对葡萄膜炎的影响及机制，为葡萄膜炎防治研究寻找到重要靶分子。

Behcet’s disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome are the two most common uveitis entities and the leading cause of blindness in China. The disorder of Th1, Th17 and Treg cells in quantity and function are critical to the development of both diseases. Recent studies found that progranulin (PGRN) had an important negative regulatory effect on immune response and our recent preliminary experiment results revealed there was a decreased expression of PGRN in active BD and VKH patients. The project is therefore designed to investigate the role PGRN in uveits and the mechanism involved in. Administration of recombinant protein of PGRN or gene deficiency are preformed in animal model to confirm the role of PGRN in the occurrence, development and prognosis of uveitis and effect of PGRN on differentiation of Th17, Th1 and Treg cells. We also use retinal pigment epithelial cells as carrier to detect the role and the possible pathway of PGRN on the local immunoregulatory cells. Collectively, the aims of these studies are to disclose the role of PGRN in the pathogenesis of uveitis and to search for new strategies for the prevention and treatment of uveitis.