雌孕激素调节滋养细胞释放微颗粒促进母胎界面免疫豁免

Deficiency of immune privilege results in the failure of early pregnancy. Immune privilege is regulated by maternal estrogen and progesterone. but the underlying mechanism remains unclear. M2 macrophages play important role in immuno- inflammatory inhibition, and abundant macrophages are found to infiltrate the feto-maternal interface. Our previous studies have shown that estrogen and progestogen can induce trophoblast cells to release microparticles (T-MPs) that promote macrophages polarize toward M2 phenotype. Based on this, we hypothesize that maternal estrogen and progesterone induced T-MP release by trophoblasts to promote M2 macrophage polarization, leading to immune privilege formation during embryo implantation. This study will be carried out through in vitro and in vivo models as well as clinical samples to dissect how estrogen and progesterone influence the release of microparticles by trophoblast cells, how T-MPs mediate M2 macrophage polarization and how M2 macrophages remodel the immune microenvironment at the feto-maternal interface. Finally, new immune therapy will be seeked to treat abnormal implantation-related early abortion. Together, this study aims to elucidate the molecular and cellular mechanism underlying the formation of immune privilege at the feto-maternal interface and try to develop new immunotherapeutic approach againt early abortion.

免疫豁免缺失是早孕失败的重要原因，其受雌、孕激素调节。然而雌、孕激素如何调节免疫豁免的相关机理仍不清楚。妊娠母胎界面存在大量巨噬细胞，而巨噬细胞转变为M2表型则能够抑制炎症与免疫。前期研究表明，雌、孕激素可以诱导滋养层细胞释放微颗粒（T-MPs），后者则能够作用巨噬细胞，使其向M2型极化。基于此，申请人提出假设：雌孕激素调节滋养细胞释放微颗粒，通过巨噬细胞促进母胎界面免疫豁免。本项目拟通过体内体外实验以及临床样本的收集来分析雌孕激素对滋养层细胞释放T-MPs的影响，T-MPs介导的M2型巨噬细胞极化对母胎界面免疫微环境的影响，进而探寻新型免疫疗法，阻止早期胚胎着床异常所致的流产。本项目有望从整体角度阐释早期母胎界面免疫豁免形成机理，为早期流产免疫治疗提供新思路。

胚胎着床及妊娠的维持是子宫内膜局部免疫平衡被打破和建立的过程，而免疫豁免缺失是早孕失败的重要原因，同时妊娠的维持与雌、孕激素密切相关。然而雌、孕激素如何调节免疫豁免的相关机理仍不清楚。妊娠母胎界面存在大量巨噬细胞，而巨噬细胞转变为M2表型则能够抑制炎症与免疫。前期研究表明，雌、孕激素可以诱导滋养层细胞释放微颗粒（T-MPs），后者则能够作用巨噬细胞，使其向M2型极化。基于此，申请人提出假设：雌孕激素调节滋养细胞释放微颗粒，通过巨噬细胞促进母胎界面免疫豁免。本项目拟通过体内体外实验以及临床样本的收集来分析雌孕激素对滋养层细胞释放T-MPs的影响，T-MPs介导的M2型巨噬细胞极化对母胎界面免疫微环境的影响，进而探寻新型免疫疗法，阻止早期胚胎着床异常所致的流产。本项目有望从整体角度阐释早期母胎界面免疫豁免形成机理，为早期流产免疫治疗提供新思路。