Deciphering the preeclampsia-specific immune microenvironment and the role of pro-inflammatory macrophages at the maternal–fetal interface

作者：Haiyi Fei, Xiaowen Lu, Zhan Shi, Xiu Liu, Cuiyu Yang, Xiaohong Zhu, Yuhan Lin, Ziqun Jiang, Jianmin Wang, Dong Huang, Liu Liu, Songying Zhang, Lingling Jiang · 发表于：eLife · 年份：2025 · DOI：10.7554/elife.100002.3 · 被引用次数：5 · 研究领域：Pregnancy and preeclampsia studies、Reproductive System and Pregnancy、Immune responses and vaccinations

Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between PE and GDM is still lacking. In this study, cytometry by time of flight indicated that the frequencies of memory-like Th17 cells (CD45RA − CCR7 + IL-17A + CD4 + ), memory-like CD8 + T cells (CD38 + CXCR3 − CCR7 + Helios − CD127 − CD8 + ) and pro-inflam Macs (CD206 − CD163 − CD38 mid CD107a low CD86 mid HLA-DR mid CD14 + ) were increased, while the frequencies of anti-inflam Macs (CD206 + CD163 − CD86 mid CD33 + HLA-DR + CD14 + ) and granulocyte myeloid-derived suppressor cells (gMDSCs, CD11b + CD15 hi HLA-DR low ) were decreased in the placenta of PE compared with that of normal pregnancy (NP), but not in that of GDM or GDM&PE. The pro-inflam Macs were positively correlated with memory-like Th17 cells and memory-like CD8 + T cells but negatively correlated with gMDSCs. Single-cell RNA sequencing revealed that transferring the F4/80 + CD206 − pro-inflam Macs with a Folr2 + Ccl7 + Ccl8 + C1qa + C1qb + C1qc + phenotype from the uterus of PE mice to normal pregnant mice induced the production of memory-like IL-17a + Rora + Il1r1 + TNF + Cxcr6 + S100a4 + CD44 + Th17 cells via IGF1–IGF1R, which contributed to the development and recurrence of PE. Pro-inflam Macs also induced the produ...