Figure 4.

Subpopulations of human dNK cells in early pregnancy and their differences in surface receptor expression profiles. Single-cell sequencing showed that dNK cells in early pregnancy were divided into three subpopulations, including dNK1, dNK2, and dNK3. dNK1 cells are CD56^bright CD49a^high KIR^high NKG2A^high LILRRB1^high CD39^high phenotype, about 55% of total dNK cells. dNK2 cells are CD56^bright CD49a⁺ KIR^low NKG2A^high LILRRB^- CD103^- phenotype, about 15% of total dNK cells. dNK3 cells are CD49a⁺ CD69^high CD103^high CD161^high KIR^low NKG2A^low NKP44⁺ NKG2D^high phenotype, about 15% of total dNK cells. Additionally, three dNK types have different degranulation capacity and IFN-γ secretion capacities in response to nonspecific stimulation. Pregnancy-trained memory NK cells (PTdNK) are found in the decidua of multiple pregnancies, like dNK1, with CD56^bright KIR^high NKG2A^high LILRRB1^high NKG2C^high phenotype. In the presence of IL-15, the interaction of NKG2C with HLA-E and LILRB1 with HLA-G induced increased amounts of IFN-γ and VEGFa secreted by PTdNK. And IFNG and VEGFA were found to have increased accessibility in PTdNK cells by ATAC-seq analysis.