排斥反应是影响肝移植成功和移植物长期存活的关键因素之一。申请者的前期研究和以及其他学者的研究已初步证实Th17细胞可通过直接或间接的作用促进排斥反应的发生。 但Th17在肝脏移植排斥反应中的作用及机制尚不明确。最新研究证实Batf可能是Th17细胞转录因子的重要调节蛋白。因此，申请者拟采用ChIP-Seq技术、凝胶电泳漂移（EMSAs）免疫共沉淀（IP）等技术，在体外实验中探讨转录调节蛋白Batf/IRF4调节Th17分化的分子机制。同时，我们将建立大鼠肝移植急性排斥反应模型，探讨Th17以及Batf/IRF4通过对Th17分化的调节作用对肝移植排斥反应发生及发展的影响。并以Batf/IRF-4 为靶点，构建shRNA慢病毒载体，初步探讨通过干预Batf/IRF-4来调节 Th17分化及效应，从而抑制排斥反应的发生与发展，为临床有效控制肝移植排斥反应提供新的治疗手段，丰富目前的免疫抑制策略

Allograft rejection, which is commomly caused by cellular immunity, is one of the most immportant reason affecting success of liver tranplantation and long-term survival of recipients. Our previous research and other scientist had reported that the Th17 cells could contibute to the development of rejection in solid organ transplantation via direct and indirect pathways. While, the regulated mechanism of Th17 cells proliferation and how does Th17 cells remained uncertain. In this programme, we will apply used ChIPseq analysis, electromobility shift assays (EMSAs), Co-Immunoprecipitation（CO-IP）to identify the interaction pattern for Batf and IRF4 and molecular mechanism of Th17 differentiation. Meanwhile, we will establish rat liver transplantation animal model to demostrate the role of Batf in regulating diferentiation of Th17 cells, and the mechnism if Th17 cell in promoting liver allograft rejection in vivo. Constuct Batf ShRNA to knockdown the transcription of Batf, and survey the immunotherapy effect of Batf/IRF-4 in regulating Th17 differentiation and inhibition or reversion of rejection. This research may increase our knowledge of cellular immunology and provide us new approaches to reduce episodes of allograft rejection for liver transplantation recipients.