Epithelial membrane protein 2 (EMP2) is a tetraspan membrane protein that has been revealed in cancer and placental models to mediate a number of vascular responses. Recently, Emp2 modulation has been shown to have an immunologic effect on uterine NK cell recruitment in the mouse placenta. Given the importance of immune cell populations on both placental vascularization and maternal immune tolerance of the developing fetus, we wanted to better characterize the immunologic effects of Emp2 at the placental-fetal interface. We performed flow cytometry of WT and Emp2 KO C57Bl/6 mouse uterine horns at GD12.5 to characterize immune cell populations localized to the various components of the maternal-fetal interface. We found that Emp2 KO decidua and placenta showed an elevated overall percentage of CD45+ cells compared to WT. Characterization of CD45+ cells in the decidua of Emp2 KO dams revealed an increase in NK cells, whereas in the placenta, Emp2 KO dams showed an increased percentage of M1 macrophages (with an increased ratio of M1/M2 macrophages). Given the differences detected in uNK cell populations in the decidua, we further characterized the interaction between Emp2 genetic KO and NK cell deletion via anti-asialo GM1 antibody injections. While the double knock-out of Emp2 and NK cells did not alter individual pup birthweight, it significantly reduced total litter weight and size by ∼50 %. In conclusion, Emp2 appears to regulate uNK and macrophage cell populations in pregnancy.

上皮膜蛋白 2 (EMP2) 是一种四跨膜蛋白，已在癌症和胎盘模型中发现可介导多种血管反应。最近，已显示Emp2调节对小鼠胎盘中的子宫 NK 细胞募集具有免疫学作用。鉴于免疫细胞群对发育中胎儿的胎盘血管化和母体免疫耐受的重要性，我们希望更好地表征Emp2在胎盘-胎儿界面的免疫学作用。我们在 GD12.5 对 WT 和Emp2 KO C57Bl/6 小鼠子宫角进行了流式细胞术，以表征定位于母胎界面各种成分的免疫细胞群。我们发现Emp2与 WT 相比，KO 蜕膜和胎盘显示 CD45+ 细胞的总体百分比升高。Emp2 KO 母体蜕膜中 CD45+ 细胞的表征显示 NK 细胞增加，而在胎盘中，Emp2 KO 母体显示 M1 巨噬细胞百分比增加（M1/M2 巨噬细胞比例增加）。鉴于在蜕膜中 uNK 细胞群中检测到的差异，我们通过抗去唾液酸 GM1 抗体注射进一步表征了Emp2遗传 KO 和 NK 细胞缺失之间的相互作用。虽然Emp2和 NK 细胞的双重敲除并没有改变个体幼犬的出生体重，但它显着降低了总窝重和大小约 50%。总之，Emp2似乎可以调节妊娠期的 uNK 和巨噬细胞群。