g., distribution of receptors, cytolytic molecules, secreted soluble factors) found among the three studies were

consistent with each other, confirming the reliability of gene arrays [42-44]. During the early stages of pregnancy, NK cells are the dominant lymphocyte in the decidua, constituting ∼70% of the total lymphocytes. Approximately 90% of dNK cells belong to the CD56brightCD16– immature phenotype [29], called immature dNK (idNK) cells, which are specialized NK cells remarkably distinct from the mature pNK (mpNK) cell subpopulation. These idNK cells function to regulate key developmental processes, including trophoblast invasion and vascular growth [29, 45]. In a previous study we found that both human RXDX-106 purchase and mice dNK cells play a key regulatory role at the maternal–fetal interface by suppressing Th17-mediated Fostamatinib supplier local inflammation, thus promoting immune tolerance [46]. Compared with mpNK cells,

idNK cells show increased expression of several genes, including inhibitory receptors, growth factors, cytokines, chemokines, and cell cycle or proliferation-related proteins [43]. On the other hand, mpNK cells were shown to have increased expression of genes related to activating receptors, costimulatory factors, and chemokines compared with idNK cells. Additionally, we showed that idNK and mpNK cells had different TF profiles; idNK cells are enriched in homeobox TFs, which may contribute to their immaturity; while mpNK cells are enriched in zinc-finger proteins, which may contribute to their cytotoxic function [29]. Hanna et al. performed a microarray analysis Racecadotril on purified dNK cells in order to generate a transcriptional profile in terms of secreted cytokines, growth factors, and chemokines thought to be crucial for placental development [45]. Several growth factor transcripts known to stimulate angiogenesis and act

as endothelial mitogens, including vascular endothelial growth factor and placental growth factor, were highly expressed in dNK cells [45]. These data highlight the superior ability of the dNK over the pNK subpopulation to secrete various mediators important for trophoblast invasion and vascular growth. Additionally, several chemokine transcripts, including Cxcl8, Ccl5, and Cxcl10, were also highly expressed in dNK cells [29, 45]. Reduced trophoblast invasion and vascular growth in the decidua are thought to be a primary defect in pregnancy [47, 48]. These situations can manifest in several different ways including fetal growth restriction, miscarriage, and preeclampsia. Genetic studies suggest that these conditions are linked to the particular combination of KIR receptors expressed on maternal dNK cells and the HLA-C genes expressed by the fetal trophoblast [45, 49].