胰岛移植是治疗终末期糖尿病的有效方法，但移植后IBMIR引起的移植物丢失是影响移植效果的关键问题受到学界重视。课题组前期研究显示ADAR1参与胰岛细胞移植后趋化因子mRNA的编辑调控可能在移植后损伤过程中发挥重要作用，但其在IBMIR损伤过程中发挥作用的机制尚未明了。基于此，本课题拟进一步研究ADAR1在胰岛移植IBMIR损伤及移植排斥中的作用机制。采用CRISPRa/i等技术研究胰岛细胞移植前后ADAR1表达及其对生物学的影响；采用IBMIR模拟系统结合临床样本和小鼠胰岛移植模型，研究ADAR1对IBMIR过程中胰岛细胞功能影响与固有免疫炎症的关系；利用CLIP结合比对组学寻找ADAR1在胰岛细胞移植物损伤过程中作用位点及靶基因编辑前后分子功能及其下游信号活化差异，寻找干预靶点，并体内验证其在移植物丢失中的作用和机制，揭示胰岛移植物损伤中的新机制，为提高胰岛移植效果提供新思路与实验数据。

Islet trasplantation is the of choice treatment for diabetes in end-stage.However, graft loss induced by IBMIR after transplantation has become a key issue affecting the effect of islet transplantation. Our previous studies showed that ADAR1 may play an important role in the editing and regulation of chemokines mRNA after islet transplantation, but the mechanism of how ADAR1 plays a role in the process of IBMIR injury is still unclear. Based on this, this study intends to further study the mechanism of ADAR1 in the IBMIR injury and rejection of in islet transplantation. CRISPRa/ I technology, qPCR and western-blot were used to study the expression of ADAR1 before and after islet transplantation and its influence on biological phenotypes, chemokines and inflammatory factors. In vitro IBMIR model combined with mouse islet transplantation model was used to study the relationship between the effect of ADAR1 on the function of islet cells during the process of IBMIR and the generation of innate immune inflammation. Using the CLIP ADAR1 in islet cells in the process of graft injury site and target molecules were analzed after gene editing and its downstream signal were verified, aims at revealing the mechanisms in islet graft injury, providing a new method to improve the effect of islet transplantation.