T Cells at the Maternal—Fetal Interface: Placental Dynamics in Healthy and Complicated Pregnancy 2260996

Abstract Introduction Deciphering the cellular dynamics that sustain tolerance and placental function in health and disease is essential for better therapies. We built a maternal—fetal placental atlas to characterize common immune-mediated pregnancy complications. Methods We collected 69 placenta samples from patients with pregnancy complications including spontaneous preterm birth (n = 10), fetal growth restriction (n = 9), pre-term preeclampsia (n = 10), term preeclampsia (n = 8), type 1 diabetes (n = 10) and healthy controls (n = 21). We profiled samples via multi-modal10x Genomics single cell sequencing: gene expression, CITE-seq and paired T cell receptor, with spatial transcriptomics (Visium HD) in a subset for validation. Results We profiled over 1.2 million placental cells, the largest atlas to date. We identified 114 cell populations, among them 15 T cell subsets. Using genetic demultiplexing we determined fetal or maternal origin of each cell. We found that the majority of the placental T cells are maternal and that the fetal T cells are only naïve or unconventional T cells (γδT cell subsets and MAIT cells). Using paired TCR-seq data we identified T cell clones and associated clonal expansions to specific T cell subsets. Conclusion This comprehensive atlas redefines the placental cellular landscape. Uncovering the different roles that the maternal and fetal T cells have in the cellular micro-environment is key for understanding mechanisms of placental dysregulation. Funding Source NIH/NIAID 1U19AI167899 Topic Categories Immune Mechanisms of Human Disease (HUM)