母胎界面免疫微环境稳态是妊娠得以建立和维持的必要保障，而复发性流产（RSA）的发生与该免疫稳态失衡相关。蜕膜巨噬细胞（dMϕ）在局部免疫功能的调节中发挥重要作用，其极化异常与RSA密切相关，但其病理机制尚不清楚。MNSFβ是一种在体内广泛表达的免疫抑制因子，参与调控巨噬细胞的凋亡和分化，但其在dMϕ极化中的作用还未见报道。我们前期工作中发现，RSA患者dMϕ中CD11chi 亚群的比例升高，MNSFβ的表达也异常增高；将RSA患者的dMϕ培养上清与人绒毛外滋养层细胞（EVT）共孵育后，EVT的侵袭活性显著减弱，而且MNSFβ能与ERα结合。由此推测： MNSFβ可能通过结合ERα，干扰雌激素/ ERα信号通路活性而影响dMϕ极化。本项目拟利用小鼠模型、细胞模型和人体组织样本，探讨MNSFβ在dMϕ极化过程中的作用及其作为RSA临床干预技术靶分子的可能性，为RSA病理机制的研究提供新线索。

Homeostasis of immune microenvironment at maternal-fetal interface is essential for the establishment and maintenance of pregnancy, and the damage on this balance could result in adverse pregnancy outcomes including the recurrent spontaneous abortion (RSA) in human. Decidual macrophages (dMϕs) play crucial roles in regulation of the local immune microenvironment, and the dysfunction of dMϕs is associated with the pathogenesis of RSA, but the exact mechanism is unknown. MNSFβ, a non-specific immunosuppressive factor widely expressed in vivo, plays important role in the regulation of macrophage differentiation and apoptosis, but its role in dMϕ polarization and activity has not been reported. It was observed previously in our lab that, the percentage of CD11chi subset of dMϕs in RSA patients was significantly higher than that of normal pregnant women, while the percentage of CD11clow subset in RSA patients was significantly lower. The expression level of MNSFβ in dMϕs of RSA patients was also significantly increased than that of normal pregnant women. In addition, the invassiveness of human extravillous trophoblasts (EVTs) incubated with the supernatant of dMϕs from RSA patients was significantly reduced compared to that of EVTs incubated with the supernatant of dMϕs from normal pregnant women. Pull-down assay showed that MNSFβ interacted with ERα. Thus, we hypothesize that, MNSFβ may modulate dMϕ polarization through the ERα signaling pathway by binding to ERα. This study are aimed to explore the mechanism underlying roles of MNSFβ in dMϕ polarization, and the potentiality of MNSFβ act as a novel target for RSA clinical intervention, by using the macrophage polarization model, animal models and human tissue samples.