母-胎界面Galectin-9/Tim-3信号异常调控NK细胞介导子痫前期发病的分子机制

Preeclampsia(PE) is a common disease during the course of pregnancy. The abnormal activation of NK cells is widely acknowledged to be involved in the onset of PE, though its precise mechanism remains unclear. Our previous study discovered that in PE patients the immune suppressive molecule Tim-3 was down-regulated on decidual NK cells, and its ligand Galectin-9 is less secreted by trophoblasts. Compared with normal pregnant women of the same trimester, decidual Tim-3+ NK cells produced more pro-inflammatory cytokines and less anti-inflammatory cytokines in PE patients, which indicates that the dysregulation of Galectin-9/Tim-3 signal on decidual NK cells participates in the mediation of PE. In this project we plan to systematically analyze the expression of Galectin-9/Tim-3 at maternal-fetal interface in both normal late pregnancy and PE patients, to elucidate the functional regulation of Galectin-9/Tim-3 signal on decidual NK cells, as well as to further compare the phenotype of decidual Tim-3+ and Tim-3- NK cells in normal pregnancy and PE patients. Thus we hope to explore the regulation of Tim-3+and Tim-3-NK cells on the biological behavior of trophoblasts and the differentiation and function of other immune cells, and the mechanism of vascular remodeling failure and maternal-fetal immune imbalance in PE patients, in order to provide new insights for the diagnosis and treatment of PE.

NK细胞异常活化介导子痫前期的发病，但其确切机制仍不明晰。我们前期研究发现免疫抑制性分子Tim-3在子痫前期蜕膜NK细胞表达下降，其配体Galectin-9在滋养细胞分泌降低；与同期正常妊娠相比，子痫前期蜕膜局部Tim-3+NK细胞产生更高水平促炎性细胞因子，而抗炎性细胞因子表达降低；提示母-胎界面Galectin-9/Tim-3信号异常可能通过调控NK细胞功能参与子痫前期发病。本研究我们拟系统分析Galectin-9/Tim-3信号在正常晚孕妊娠与子痫前期母-胎界面的表达特征，解析Galectin-9/Tim-3信号对蜕膜NK细胞的亚群分化及功能调控的作用，探讨正常妊娠与子痫前期Tim-3+NK与Tim-3-NK细胞对滋养细胞生物学行为以及其它免疫细胞亚群分化与功能的调节作用，解析子痫前期胎盘血管重铸障碍与母-胎免疫耐受失衡机制，为子痫前期的早期预警与防治提供新思路。