子痫前期(PE)是一种母体适应性免疫和固有免疫均过度激活的胎盘源性疾病。单核/巨噬细胞是连接这两种免疫反应的桥梁，且在胎盘形成中发挥着重要作用。课题组前期从适应性免疫和固有免疫角度对PE的发病机制进行了系列研究，近期发现PE外周血中“促炎型”单核细胞明显增加，且与疾病严重程度密切相关。另有研究表明，PE患者外周单核细胞易在子宫局部分化为促炎型(M1型)蜕膜巨噬细胞(DM)，而非免疫调节型(M2型)DM。然而，调节DM向M1或M2型极化的原因和机制尚不是十分清楚。PD-1和Tim-3是重要的负性调节信号分子，它们参与巨噬细胞极化的调节。我们推测：PD-1/Tim-3调控早期妊娠中DM极化参与PE的发生。本项目通过临床现象观察、体外实验和动物模型三个方面，延续探讨PE中调节DM极化的原因、分子机制，以及以PD-1/Tim-3为靶点的治疗效果。为深入研究PE发病机制和其防治提供新思路和新靶点。

Pre-eclampsia (PE) is a placenta-originated disease characterized by over-activation of maternal adaptive immunity and innate immunity. Monocyte/macrophage are the bridges of the two kinds of immunity, which play a critical role in the development of placenta. Our team has undertaken a series of studies on the pathogenesis of PE in view of the adaptive immunity and innate immunity. Our recent findings show that the pro-inflammative subsets of peripheral monocytes increased in PE patients, and were closely correlated with its severity. The published studies indicated that the peripheral monocytes in PE were easily differentiated into the pro-inflammative subsets of macrophages in deciduas (namely, M1 subset), but not into the immune-regulative subsets (M2 subset). And the new researches have shown that the biased polarization of macrophages is related with some diseases in humans. However, it remains unclear about the factors and mechanism on regulating the polarization of DM to M1 or M2 subsets. PD-1 and Tim-3 are important negative regulative signals, which can regulate the polarization of DM. As a result, we hypothized that the dysregulation of DM polarization by PD-1/Tim-3 at the first trimester of gestation would participate in the pathogenesis of PE. In this study, by clinical observation, in-vitro study and animal model experiments, we continue to determine the factors that regulate the DM polarization and its mechanism. Moreover, by setting up PE-like animal model, we further investigate the therapeutic effects by targeting PD-1/Tim-3 signals. We aim to elucidate the important molecular immunological mechanism of PE, to discover the potential therapeutic target, and to provide supporting evidence for the clinical prevention and treatment of PE.