Behcet病是累及多器官、多系统的自身炎症性疾病。目前认为遗传因素、免疫紊乱在其发病中起重要作用，其机制尚不完全清楚。最近我们发现IL23R与Behcet病显著相关，精细定位发现疾病相关多态为rs17375018，且为功能性多态，可能上调IL23R基因转录。文献报道IL23R是TH17终末分化的必要分子。据此推测IL23R多态可能调控蛋白表达，进而影响TH17细胞分化、功能并导致该病发生。为证实此假设，本研究以rs17375018多态为切入点，探讨该多态对IL23R基因转录功能的影响，以阐明此多态生物学功能；研究此多态对TH17分化、成熟和功能影响，以明确其免疫学功能；通过检测STAT3及RORγt通路中分子磷酸化水平，阐明该多态影响TH17分子机制； 通过此研究将可能揭示IL23R多态通过何种机制参与Behcet病发生这一科学问题，为Behcet病个体化防治提供新靶点。

Behcet's disease (BD) is a multi-systemic autoinflammation disease mainly mediated by genetic predisposition, infections and immunological abnormalities. However the mechanism is still undetermined. Recently we showed that IL23R was identified as a susceptibility gene of BD in a Han Chinese population. It was reported that rs17375018 SNP in IL23R gene controlled this gene expression. Besides the priming of T cells with its ligand, IL23R controlled the activation of macrophages and TH17 cell and contributed to initiation of innate immune responses as well as the subsequent induction of adaptive immune responses. Therefore, we propose that IL23R polymorhpims control its expression, subsequent TH17 cell activation and contribute to the BD development. To test this hypothesis, we determine to study the role of IL23R polymorphism in activation of TH17 cell in the development of BD. The project mainly includes three parts as follow. (1) Expression of IL23R will be investigated to study influence of rs17375018 variant on IL23R translations. (2) Phenotype, mature and functional properties of TH17 cell will be explored to determine the role of IL23R in TH17 cell activation. (3) Activation status and interaction of STAT3 and RORγt with IL23R and effect of STAT3, RORγt on the activation of a reporter for this pathway will be determined to study the underlying mechanism of IL23R on the activation of TH17 cell in Behcet's diseases. The incidence and severity of experimental autoimmune uveitis (EAU),phenotype,mature and functional of TH17, and freqencies of Th17 will be assessed to study the role of IL23R in EAU. These studies are expected to gain a deep insight into the initiating mechanisms involved in BD from IL23R and to provide a new strategy in the prevention and treatment for this disease.