Behcet病、VKH综合征是我国致盲率最高的葡萄膜炎类型，Th1/Th17/Treg细胞功能和数量异常是其发病基础，上述三种细胞失衡可上溯至树突状细胞（DC）活化及功能异常。我们最近预实验发现A20在活动期Behcet患者中表达显著降低，而且A20基因多态与Behcet病和VKH综合征显著相关。本项目以这两种疾病为研究对象，探讨A20在这两种患者DC中的表达水平、A20对DC活化、功能状态以及对Th1、Th17和Treg细胞分化的影响；探讨TLR信号通路中MAPK（P38、ERK1/2、JNK）的磷酸化水平和NLRP3炎症小体的表达等来确定A20对DC影响的机制；通过对A20的干预来探讨A20对动物模型葡萄膜炎的严重程度的作用；探讨A20基因变异对其本身基因翻译和结构、DC活化和功能、动物模型葡萄膜炎的影响。本研究旨在以A20为出发点阐明这两种不同性质疾病的发病机制，为其防治提供新策略。

Behcet's disease(BD) and Vogt-Koyanagi-Harada(VKH) syndrome are the two most common uveitis entities that lead to blindness in china. The imbalance of the number and function between effectory and Treg cells play a critical role in the pathogenesis of the two diseases. DCs play critical role in the differention and fucntion of different Th cells. Our preliminary studies showed that A20 was significantly decreased in the PBMCs from active BD patients as compared with that from inactive BD patients and normal controls, and there was a strong association between the gene polymorphisms of A20 with Behcet's disease and VKH disease. The goal of this project was to investigate the role of A20 in the pathogenesis of the aforementioned two uveitis entities. First, we will study the expression of A20 in the Mo-DC from BD patients and VKH patients to explore whether A20 was associated with the activity of the two uveitis. Secondly, we will investigate the effect of A20 on the differentiation, maturation and function of DCs and the subsequent different Th1, Th17 and Treg cell differentiation. Thirdly, we are going to study the effect of A20 on the phosphorylation of P38, ERK1/2 and JNK and the expression of NLRP3 inflammasome to clarify the mechanism involved in A20-mediated effect on DCs. Fourth, we will investigate the effect of A20 on the severity of experimental antoimmune uveitis(EAU) to validate the regulatory role of A20 in uveitis. Finally, we will assess the possible role of associated genetic polymorphisms in the expression and structure of A20, the activation and function of DCs. These studies are expected to clarify the pathogenesis of the two uveitis and provide a novel strategy in the prevention and treatment for these diseases.