本课题基于申请者前期发现术后急性排斥者移植肝组织内表达Foxp3+和IL-17+细胞均增加，Treg和Th17的表型和功能与肝脏损伤之间存在相关性，推测移植肝内微环境可能促进部分Foxp3+细胞转化为Foxp3+IL-17+细胞，加重排斥反应，影响疾病的进展。本课题拟进一步分析肝组织内Foxp3+和IL-17+表达模式，探讨肝脏微环境调控Foxp3+/IL-17+表达导致肝脏损伤的机制，同时观察肝移植术后疾病自然进程中Treg和Th17频率和功能的变化规律。体外观察肝移植中Treg转化为Th17以及对Th17的调节作用。建立肝移植急性排斥动物模型，研究利用Treg和anti-IL-17防治排斥反应的可行性。本研究不但有助于理解肝组织内Treg/Th17失衡，阐明肝移植急性排斥反应的免疫学机制，而且有可能发现辅助诊断肝移植术后急性排斥反应的免疫学指标，以及治疗排斥反应发生的新方法。

The application subject is based on our previous founding that the numbers of expressing Foxp3+ or IL-17+ cells on the allograft tissue increase obviously with acute rejection in liver transplant patients, and the phenotype and function of Treg and Th17 cells are associated with the injury of liver function. From the previous discovery, we speculate that allograft environment would improve part of Foxp3+ cells convert to the Fxop3+IL-17+ double positive cells, then increase acute rejection and affect the progress of liver disease. This subject will analysis the expression pattern of Foxp3+ and IL-17+ in liver tissue, demonstrate the mechanism of liver tissue microenvironment regulation on Foxp3+/IL-17+ expression and induction the impairment for allograft. Also, we analysis the regular patterns of frequency and function of Treg and Th17 cells in disease progress after liver transplantation. Furthermore, we will illustrate the possibility of Treg convert to the Th17 cells and regulation of Treg on Th17 cells in vitro. Finally, we will establish the liver transplant animal model to demonstrate the feasibility of using Treg and anti-IL-17 for prevention and treatment of rejection. The application subject will not only help understanding the imbalance of Treg/Th17 in liver tissue, demonstrating the immunological mechanism of acute rejection, but also to find the immunological indexes for aided diagnosis of acute rejection, and novel strategy for treatment of rejection.