Division of Neonatology and Developmental Biology, Department of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, MDCC B2-411, Los Angeles, CA, 90095, USA.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, 4525 MacDonald Research Laboratories, Los Angeles, CA, 90095, USA.
J Reprod Immunol. 2021 Jun;145:103309. doi: 10.1016/j.jri.2021.103309. Epub 2021 Mar 9.
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，在癌症和胎盘模型中被揭示可介导多种血管反应。最近，Emp2 调节已被证明对小鼠胎盘中的子宫 NK 细胞募集具有免疫作用。鉴于免疫细胞群对胎盘血管生成和母体对发育中胎儿的免疫耐受都很重要，我们希望更好地描述 Emp2 在胎盘-胎儿界面的免疫作用。我们对 WT 和 Emp2 KO C57Bl/6 小鼠子宫角在 GD12.5 时进行流式细胞术，以表征定位于母体-胎儿界面各个成分的免疫细胞群。我们发现，与 WT 相比，Emp2 KO 蜕膜和胎盘的 CD45+细胞总体百分比升高。对 Emp2 KO 母鼠蜕膜中 CD45+细胞的特征分析显示 NK 细胞增加，而在胎盘上，Emp2 KO 母鼠 M1 巨噬细胞的百分比增加（M1/M2 巨噬细胞的比例增加）。鉴于在蜕膜中检测到 uNK 细胞群的差异，我们通过抗-asialo GM1 抗体注射进一步表征了 Emp2 基因 KO 和 NK 细胞缺失之间的相互作用。虽然 Emp2 和 NK 细胞的双重敲除并未改变单个幼崽的出生体重，但它显著降低了总产仔体重和大小约 50%。总之，Emp2 似乎调节妊娠期间的 uNK 和巨噬细胞细胞群。
