HLA-G/ILT2调控蜕膜多形核髓系抑制细胞分化促进妊娠维持的机制研究

蜕膜多形核髓系抑制细胞（PMN-MDSC）是母胎界面细胞交互对话网络重要成员，其数量减少及功能异常与不明原因复发性流产（URPL）等不良妊娠结局密切相关，然而蜕膜PMN-MDSC功能及调控机制尚未阐明。我们前期研究发现早孕蜕膜存在一群ILT2+PMN-MDSC，滋养细胞表达HLA-G，HLA-G可与ILT2结合并诱导蜕膜PMN-MDSC表达TGF-β等免疫调节分子。鉴于此，我们提出假说：HLA-G/ILT2信号轴在调控蜕膜PMN-MDSC向有利于妊娠的免疫调节表型及功能方向分化中发挥关键作用。为了验证这一假说，本项目拟在前期研究的基础上，通过体外模拟母胎界面免疫微环境，并利用适当的动物模型，研究HLA-G/ILT2信号轴调控蜕膜PMN-MDSC表型及功能的分子机制，以期深入阐明滋养细胞与蜕膜PMN-MDSC之间的交互对话机制，为URPL等相关疾病的防治提供新的靶点。

Decidual polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) is an important part of the maternal-fetal crosstalk. The decrease and dysfunction of PMN-MDSC are closely related to adverse pregnancy outcomes such as unexplained recurrent pregnancy loss (URPL). However, the function and regulation mechanism of decidual PMN-MDSC have yet been elucidated. Our preliminary experiments showed that there was a group of ILT2+ PMN-MDSC in the decidua of early pregnancy. Trophoblasts expressed HLA-G. HLA-G could bind to ILT2 and induce the expression of TGF-β and other immune regulatory molecules in decidual PMN-MDSC. Based on these findings, we hypothesize that HLA-G/ILT2 signal plays a key role in regulating decidual PMN-MDSC differentiation into immune regulatory phenotype and function in favor of pregnancy. In order to demonstrate this hypothesis, based on our preliminary experiments, we will use in vitro models simulating the immune microenvironment of maternal-fetal interface and appropriate animal models to study the molecular mechanisms of HLA-G/ILT2 signal regulating the phenotype and function of decidual PMN-MDSC. We hope to elucidate the mechanisms of crosstalk between trophoblasts and decidua PMN-MDSC, further providing novel targets for the prevention and treatment of URPL and related diseases.