母胎微环境NK细胞调节胚胎免疫耐受与免疫排斥机制研究

母体因为免疫耐受容受胚胎，因为免疫排斥导致流产，早孕蜕膜中的NK细胞高达70%在其中发挥重要作用。我们发现蜕膜NK细胞有多种亚群，CD27+NK细胞参与胚胎免疫耐受，CD11b+NK细胞参与胚胎免疫排斥，CD49a+Eomes+NK细胞促进胚胎发育。近期，我们进一步发现人蜕膜CD49a+NK与CD49a-NK细胞可能与免疫耐受和免疫排斥直接相关，我们将试图证明：1、蜕膜CD49a+NK细胞通过自身NKG2A、KIRs，分别与来自胚胎绒毛外滋养层细胞的HLA结合，接收其容受性教育，介导母胎免疫耐受；2、未经绒毛外滋养层细胞HLA教育的CD49a-NK细胞，在母胎界面被多种活性分子激活，转化为GM-CSF+炎症性NK细胞，打破免疫耐受，介导母胎免疫排斥；3、蜕膜CD49a+和CD49a-NK细胞分别介导母胎免疫耐受和免疫排斥的分子机制、发育分化与转录调控机制，以及可能存在的两者相互转换机制。

Immune tolerance causes maternal endometrial receptivity effects of the successful pregnancy, whereas immune rejection causes miscarriage. Decidual NK cells, which take as high as 70% of lymphocytes in early deciduas, play a key role in regulating immune response. We have found that decidual NK cells have a variety of subgroups: CD27+ NK cells have been involved in immune tolerance; CD11b+ NK cells have been involved in embryo immune rejection; CD49a+Eomes+ NK cells promote embryonic development. Recently, we further found that human decidual CD49a+ NK cells and D49a- NK cells may have direct relationship with immune tolerance and immune rejection. We will try to investigate that: 1. Decidual CD49a+NK cells, which have cross-talk with HLAs on fetal trophoblast cells through NKG2A/KIRs, are re-educated for the maternal endometrial receptivity effects and involved in maternal-fetal immune tolerance; 2. Decidual CD49a-NK cells, which have not experienced re-education through cross-talk with HLAs on fetal trophoblast cells, are activated by a variety of active molecules at the maternal-fetal interface and further transformed into GM-CSF+ inflammatory NK cells. These CD49a-NK cells break the immune tolerance and mediate maternal-fetal immune rejection; 3. Decidual CD49a+ NK cells and CD49a-NK cells mediated the molecular mechanism, the differentiation and transcriptional regulation mechanism of maternal-fetal immune tolerance and immune rejection respectively. It is possible that these two decidual NK subsets have mechanism of conversion between each other.