Deficiency of PD-L1+ Non-Immune Cells in Preterm Labor

The objective of this study was to characterize the cells at the maternal-fetal interface (MFI) in term and preterm pregnancies, each in the laboring and non-laboring state. Using mass cytometry to obtain single-cell resolution, we identified 31 cell populations at the MFI, including 25 immune cell types and six non-immune cell types. Among the immune cells, maternal PD1+ CD8 T cells subsets were less abundant in term laboring compared to term non-laboring. Among the non-immune cells, PD-L1+ maternal (stromal) and fetal (extravillous trophoblast) cells were more abundant in term laboring compared to preterm laboring pregnancies. Consistent with these observations, the expression of CD274, the gene encoding PD-L1, was significantly depressed and less responsive to fetal signaling molecules in cultured mesenchymal stromal cells from the decidua of preterm compared to term pregnancies. Overall, these results suggest that the PD1/PD-L1 pathway at the MFI may perturb the delicate balance between immune tolerance and rejection and contribute to the onset of spontaneous preterm labor.

本研究旨在表征足月妊娠与早产妊娠，且分别处于分娩与未分娩状态下的母胎界面（maternal-fetal interface, MFI）细胞特征。本研究借助质谱流式细胞术（mass cytometry）获取单细胞分辨率数据，最终在母胎界面鉴定出31种细胞群，其中包含25种免疫细胞类型与6种非免疫细胞类型。针对免疫细胞的分析显示，与足月未分娩组相比，足月分娩组的母体PD1+ CD8 T细胞亚群丰度更低。针对非免疫细胞的分析则表明，与早产分娩组相比，足月分娩组的PD-L1+母体（基质）细胞与胎儿（绒毛外滋养层）细胞丰度更高。与上述观察结果一致的是，对取自早产妊娠组蜕膜的培养间充质基质细胞进行分析发现，相较于足月妊娠组，该组中编码PD-L1的CD274基因表达水平显著下调，且对胎儿信号分子的应答反应更弱。综上，本研究结果提示母胎界面的PD1/PD-L1通路可能会扰乱免疫耐受与免疫排斥间的微妙平衡，并参与自发性早产分娩的发生。