Single-cell immune profiling of third trimester pregnancies defines importance of chemokine receptors and prevalence of CMV-induced NK cells in the blood and decidua

To understand the immunological landscape in pregnancy, we performed a multiplexed cell-surface proteome screen of >350 markers on NK cells, CD4+, CD8+ and γδ T cells, B cells and monocytes in pregnant peripheral blood, cord blood and decidua, and scRNAseq, including 130 CITE-seq antibodies, on NK cells from the blood and decidua. In pregnancy, NK cells had increased AREG, SOCS1, HLA-D family gene expression, and increased CCR5 and HLA-DR, and decreased CD9, CD36, and CX3CR1 at the protein level.

Pregnancy caused a shift toward higher frequencies of CD56bright cells in the blood caused by a numerical reduction in CD56dim cells. We demonstrate a role for chemokine receptor CX3CR1 in NK cell activation and define a subset of cytomegalovirus-induced decidual NK cells. Overall, this study provides key insights on NK cell immunity in pregnancy and reveals fundamental differences in the NK cell compartment during gestation.