诱导移植物特异的免疫耐受是移植免疫学家长期以来面临的最大挑战。肝脏长期以来被认为是免疫特惠器官，与心肾相比，肝移植免疫排斥反应较轻，在小鼠，同种异体肝移植能够突破MHC的限制，诱导移植物先天的免疫耐受。肝脏这种固有的致耐受源性的特性至今仍未被揭开。本课题组最近的研究结果表明肝脏树突状细胞（DC）和Foxp3+CD4+CD25+ 调节性T细胞（Treg）在肝移植耐受中起重要作用，其机理还不十分清楚。本项目利用转基因小鼠，先进的细胞分子生物学和显微外科技术，小鼠肝移植自发耐受模型与小鼠心脏移植急性排斥模型进行对比，对肝移植耐受的细胞及分子免疫学机制进行深入细致的研究，揭示肝脏特有的能够诱导Treg的抗原提呈细胞（APC）亚型及其关键的信号调节通路。本研究结果将为肝脏免疫学奠定新的理论基础，为系统免疫耐受的诱导和新的免疫抑制药的研发提供新的靶点和切入点，对临床器官移植的免疫治疗有重要的指导作用。

Induction of organ specific immune tolerance is a big challenge for transplant surgeons and immunologists worldwide. Liver has long been considered an immune privileged organ. Unlike heart and kidney,liver transplantation has less severe immune rejection. Liver allografts in mice across MHC barriers are spontaneously accepted without requirement for immunosuppression. The underlying mechanism of liver inherent tolerogenecity is still unclear. Our recent studies have demonstrated that liver dendritic cell（DC）and Foxp3+CD4+CD25+ regulatory T cells ( Treg ) play an important role in the induction of liver spontaneous transplant tolerance. In this project, we will employ transgeneic mice, advanced cellular and molecular technologies, precised microsurgery techniques, as well as mouse spontaneous liver transplant tolerance model and acute rejection of heterotopic heart transplantation model,to critically investigate the insight mechanisms of liver tolerance, to elucidate the key cell type among liver inherent antigen presenting cells (APC) and its molecular signaling pathways which is responsible for the Treg expension and liver transplant tolerance induction.The results from our study will further reveal the cellular and molecular mechanism of liver spontaneous transplant tolerance, will guide the clinical approaches of prevention or treatment of allograft rejection, and will identify a potential target for the development of immunosuppressive drug.