蜕膜NK细胞（dNK）是母-胎界面最主要的免疫细胞，目前在蜕膜局部的来源还不完全清楚。研究表明，ESC自噬水平于分泌期升高，但是这种高自噬对母-胎免疫微环境是否具有调节作用还不清楚。申请人前期实验发现蜕膜基质细胞（DSC）与子宫内膜间质细胞（ESC）相比自噬水平升高，表达更高水平的黏附分子，对dNK的黏附能力更强，同时ESC自噬升高后TNF家族分子HVEM表达增加，自噬抑制剂3-MA可降低孕鼠子宫局部NK细胞比例，并促进胚胎丢失。因此本项目拟以体外模拟蜕膜微环境和体内动物实验为研究手段，研究子宫蜕膜化进程中的自噬特征和NK细胞驻留分布特征；自噬调节ESC/DSC黏附分子表达的机制以及对NK细胞在子宫局部驻留的影响；蜕膜自噬-NK细胞驻留异常对妊娠结局的影响，以期阐明早孕时DSC的高自噬引导dNK在蜕膜局部富集的分子机制，有助于母-胎免疫耐受机制的完善，为反复自然流产的临床防治提供新思路。

As the main DICs at the maternal-fetal interface, the origin of dNK cells is still under debate. Studies found that ESC autophagy is increased in the secretory phase during the menstrual cycle. However, the effect of such high level of autophagy on the regulation of maternal-fetal immune microenvironment is still not clear. Preliminary experiments showed that compared to ESCs, autophagy was increased in DSCs, with higher expression of adhesion molecules and stronger adhesion ability to dNK cells. Meanwhile, HVEM, one of TNF superfamily member, was elevated in autophagy increased ESCs. Therefore, taking advantage of in vitro trials for imitating the microenvironment of decidua and in vivo animal experiments, our study intends to investigate: 1) the characteristics of ESC/DSC autophagy and NK cell distribution during decidualization; 2) the regulatory mechanism of autophagy to ESC & DSC adhesion ability; 3) the effects of autophagy-regulated ESC & DSC adhesive ability on NK cell residence; 4) the impacts of aberrant decidua autophagy and NK cell accumulation on pregnancy outcomes. This project will help to elucidate the mechanism of dNK residence in decidua via DSC autophagy in early pregnancy, provide a new direction for the theory of maternal-fetal immune tolerance, and provide a scientific basis for finding a new strategy to prevent spontaneous abortion.