调节性DC（DCreg）是诱导免疫耐受的关键细胞。如何高效、稳定地调控DCreg的分化并诱导移植耐受是肝移植领域的研究热点。前期研究发现，RIG-1可调控Jak-STAT信号通路；而JAK-STAT通路对调控DCreg分化有重要作用。我们预实验显示：抑制RIG-1能够促进DC分化为DCreg，延长移植物的存活。由此我们推测，抑制RIG-1能够阻断JAK-STAT信号通路促进DC向DCreg分化，进而诱导肝移植免疫耐受。本课题拟采用RIG-1敲除小鼠建立肝移植模型，观察移植物存活情况，体内、外实验检测RIG-1对DCreg分化的影响；进而在分子水平上检测RIG-1对Jak-STAT通路的调控作用，并利用RIG-1和Jak2双敲除小鼠观察是否具有依赖性；最后在临床上验证调控DCreg分化诱导肝移植持久免疫耐受的可行性。本项目旨在寻找一种干预移植排斥反应的新方法，提供特异性诱导免疫耐受的新思路。

Regulatory dendritic cells（DCreg）play an important role in improving long-term survival of the transplant recipient. How to use DCregs more efficiently and stably to induce transplant tolerance is the hot topic in the field of liver transplantation. Previous studies showed that RIG-1 could regulate Jak2 expression at transcriptional level, which could inhibit DCreg differentiation and induce rejection. Moreover,we showed that the inhibition of RIG-1 could prolong the allograft survival in murine liver transplant model. Therefore, we hypothesize that blocking of RIG-1 may regulate DCreg function through Jak-STAT pathway and induce liver transplant tolerance. In the current study, we aim to establish the liver transplant model using Regulatory RIG-1 knockout mice, observe allograft survival, analyze the infiltrating DC function and sort themout for RNA-Sequencing, test the effect of RIG-1 on DCreg differentiation in vitro and in adoptive transfer model in vivo, verify how RIG-1 regulate the Jak2 expression and whether the function of RIG-1 depends on Jak-STAT pathway using RIG-1 Jak2 double conditional knockout mice, finally exploit the potential of RIG-1 as a biomarker in thediagnosis of transplant rejection andDCregsinduce transplant tolerancein patients. The project will help to expand our understanding in the mechanism of transplant rejection, and provide a novel potential target for the clinical treatment of immune rejection and induction immune tolerance.