CMV-miRNA调控NKG2A/NKG2C促进巨细胞病毒抗白血病的作用和机制研究

如何降低造血干细胞移植术后白血病复发是移植免疫研究重点，造血干细胞移植后巨细胞病毒(CMV) 激活与降低白血病复发相关，推测存在巨细胞病毒介导的抗白血病作用，但细胞学机制不清。课题组前期研究发现病毒激活后的CMV-miRNA（CMV-miR-US4-1/UL-148D）(1)是降低白血病复发的独立危险因素、(2) 潜在靶向NK细胞NKG2A/NKG2C信号、(3) 影响NKG2C+NK重建；推测CMV-miRNA通过调控NK细胞发挥抗白血病作用。基于前期工作，本项目拟以CMV-miRNA调控NK细胞亚群功能为研究CMV抗白血病作用切入点，以CMV感染调控NK体外杀伤实验、人源化白血病小鼠为研究模型，借助临床队列验证，探讨CMV-miRNA调控激活NKG2C+NKG2A-NK细胞亚群，促进NK细胞杀伤白血病的作用和机制。本项目的实施有望为开辟移植后白血病复发防治新方法奠定基础。

Cytomegalovirus (CMV) activation after hematopoietic stem cell transplantation is associated with reduced relapse of leukemia, suggesting cytomegalovirus-mediated anti-leukemia effect, but the cellular mechanism remained unclear. Our previous study found that CMV-miRNA (CMV-miR-US4-1/UL-148D) after CMV activation was an independent risk factor for leukemia relapse, CMV-miRNA could potentially target NK cells NKG2A / NKG2C, CMV infection prompted NKG2C + NK reconstitution. Based on our previous work, this study is intended to clarify the CMV-miRNA regulation on NK cell subsets and the role of regulation in CMV anti-leukemia-effect. By in vitro CMV-infected cells and human leukemia mice , we want to confirm the CMV-miRNA regulation dominate activation of NKG2C + NKG2A-NK cell subsets, which promote NK cell-mediated anti-leukemia. The result might provide foundation for the development of new methods in prevention and treatment of leukemia after transplantation.