Placental intervillous blood harbors NK cells with distinct tissue-resident characteristics

The placental intervillous space is a unique immunological niche where circulating maternal immune cells come into direct contact with the fetal syncytiotrophoblast. While adaptations in immune cell composition are known to occur in the maternal decidua throughout pregnancy, it remains unclear whether similar changes take place in the intervillous space. Here, we demonstrate that the intervillous immune cell composition undergoes dynamic changes during pregnancy, with a decreased proportion of NK cells and an increased proportion of T cells from second trimester to term pregnancy. Interestingly, second-trimester intervillous NK cells were predominantly CD56^brightCD16^- with high expression of CD49a, CD103, and CD69. This phenotype more closely resembled tissue-resident decidual NK (dNK) cells than peripheral NK cells. Conditioned medium from fetal villous tissue did not induce changes in peripheral NK cell phenotype, suggesting that the observed phenotypic alterations are not driven by soluble factors from the villous microenvironment. Analysis of predicted ligand-receptor complexes suggested that NK cells may provide important growth signals to the syncytiotrophoblast. In conclusion, immunological adaptations occur in the intervillous space throughout pregnancy and the presence of dNK-like cells in the intervillous space underscores a potential role for these cells in maintaining a balanced immune environment at the maternal-fetal interface.