Single-cell RNA sequencing reveals systemic and placental immune landscape in preeclampsia

Preeclampsia (PE) is one of the most severe complications of pregnancy characterized by systemic and placental inflammation. Recently, studies have characterized the immune landscape in preeclampsia at single-cell level, further investigation is needed to understand spatial differences across placental compartments and disease subtypes.

We utilized single-cell RNA sequencing to profile the immune cells of peripheral blood and placenta compartments from early- and late-onset PE (EPE/LPE), as well as normotensive controls.

Our data revealed significant differences in immune cell composition and proportions across peripheral blood and various placenta compartments. Additionally, we found that PE patients exhibited distinct immune cell distributions and gene expression profiles compared to normotensive controls. Moreover, the frequencies and functional states of immunocytes varied between EPE and LPE patients. When subclustered major immune cells, we discovered a reduction of regulatory T cells in peripheral blood of PE patients. Hofbauer cells were almost absent in placental villi of EPE pregnancies. Furthermore, we identified a novel subset of CD8⁺ naïve T cells in peripheral blood, exclusively present in EPE, and a new subset of dNK4 cells in basal plate, which were significantly decreased in EPE.

Our study offers a comprehensive single-cell immune profile of peripheral blood and placental compartments, reinforcing the heightened pro-inflammatory environment observed in PE pregnancies. Furthermore, our analysis reveals distinct immunological differences between EPE and LPE. These findings provide potential insights for early prediction and therapeutic interventions in these disordered pregnancies.