Revealing an enhanced cytotoxic immune microenvironment at the human maternal-fetal interface in preeclampsia

Preeclampsia is a multifactorial pregnancy complication characterized by hypertension and immune dysregulation, which can lead to adverse maternal and fetal outcomes. Decidual immune cells are critical for pregnancy homeostasis, yet their functional abnormalities and mechanisms in preeclampsia remain poorly understood. Herein, we sorted decidua immune cells from preeclampsia patients for single-cell RNA sequencing to characterize cellular composition and functional heterogeneity. We delineated the immune cell landscape of the decidua in preeclampsia. A hallmark of decidual immune microenvironment in preeclampsia was the marked augmentation of cytotoxic activity. Both NK and T cells exhibited enhanced cytotoxic activity, characterized by the significant upregulation of cytotoxicity-associated genes. NK cells exhibited a differentiation predisposition toward a unique tissue-resident ITGAE⁺CD160⁺ subset with heightened cytotoxic and chemokine gene expression. Cell-cell communication analysis further revealed strengthened interactions between NK cells and macrophages, with macrophage-derived SPP1 signals potentially contributing to the amplification of local cytotoxic responses. Collectively, this study provides a comprehensive single-cell analysis of cytotoxic immune changes at the maternal-fetal interface in preeclampsia, revealing enhanced cytotoxicity that may represent a key pathological mechanism. These insights may inform the development of diagnosis and therapeutic strategies targeting cytotoxic immune dysregulation in PE.