Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA.
Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila, Manila, Philippines.
Commun Biol. 2024 Aug 23;7(1):1041. doi: 10.1038/s42003-024-06740-2.
Chorion trophoblasts (CTCs) and immune cell-enriched decidua (DECs) comprise the maternal-fetal membrane interface called the chorio-decidual interface (CDi) which constantly gets exposed to maternal stressors without leading to labor activation. This study explored how CTCs act as a barrier at CDi. The roles of human leukocyte antigen (HLA)-G and progesterone receptor membrane component 2 (PGRMC2) in mediating immune homeostasis were also investigated. The CDi was recreated in a two-chamber microfluidic device (CDi-on-chip) with an outer chamber of primary DECs and immune cell line-derived innate immune cells and an inner chamber of wild-type or PGRMC2 or HLA-G knockout immortalized CTCs. To mimic maternal insults, DECs were treated with lipopolysaccharide, poly(I:C), or oxidative stress inducer cigarette smoke extract. Expression levels of inflammation and immunity genes via targeted RNA sequencing, production of soluble mediators, and immune cell migration into CTCs were determined. In CDi-on-chip, decidua and immune cells became inflammatory in response to insults while CTCs were refractory, highlighting their barrier function. HLA-G and PGRMC2 are found to be vital to immune homeostasis at the CDi, with PGRMC2 serving as an upstream regulator of inflammation, HLA-G expression, and mesenchymal-epithelial transition, and HLA-G serving as a frontline immunomodulatory molecule, thus preventing fetal membrane compromise.
绒毛滋养层细胞（CTCs）和富含免疫细胞的蜕膜（DECs）构成了母体-胎儿膜界面，称为绒毛-蜕膜界面（CDi），它不断暴露于母体应激源而不导致分娩激活。本研究探讨了 CTC 如何作为 CDi 的屏障。还研究了人类白细胞抗原（HLA）-G 和孕激素受体膜成分 2（PGRMC2）在介导免疫稳态中的作用。使用具有源自初级 DEC 和免疫细胞系的先天免疫细胞的外室和野生型或 PGRMC2 或 HLA-G 敲除永生化 CTC 的内室的两室微流控装置（CDi-on-chip）重现 CDi。为了模拟母体损伤，用脂多糖、聚（I：C）或氧化应激诱导剂香烟烟雾提取物处理 DEC。通过靶向 RNA 测序确定炎症和免疫基因的表达水平、可溶性介质的产生以及免疫细胞向 CTC 的迁移。在 CDi-on-chip 中，蜕膜和免疫细胞在受到刺激时会变得炎症，而 CTC 则具有抗炎症性，突出了它们的屏障功能。发现 HLA-G 和 PGRMC2 对于 CDi 处的免疫稳态至关重要，PGRMC2 作为炎症、HLA-G 表达和间质-上皮转化的上游调节剂，而 HLA-G 作为一线免疫调节分子，从而防止胎儿膜受损。
