Studys on the effect of decidual stromal cells and trophoblast cells on cytokine secretion by decidual NK cells

Unexplained recurrent pregnant loss (URPL) is associated with immune imbalance at the maternal-fetal interface. Decidual immune cells regulate the response of the maternal immune system to the fetus. However, the effect of decidual stromal cells (DSCs) and trophoblast cells on cytokine secretion by decidual NK cells remains unclear. In this study, we investigated the influence of JEG-3 cells and DSCs on the secretion of cytokines in dNK cells. Furthermore, we investigated whether or not cytokine secretion was regulated by the mitogen-activated protein kinase (MAPK) signaling pathway at the maternal-fetal interface. Our study showed that the secretions of both IFN-γ and TNF-α in dNK cells in URPL were significantly higher than those in normal pregnancy. In the coculture of JEG-3, DSCs, and dNK cells, IL-10 and IL-4 production increased in dNK cells during normal pregnancy; whereas IFN-γ and TNF-α production increased but IL-10 and IL-4 levels decreased during URPL. Furthermore, pretreatment with P38/MAPK inhibition significantly inhibited the secretion of NK1- and NK2-type cytokines in the coculture of the three types of cells. Our study elucidated the influence of trophoblasts and DSCs on the expression of cytokines in dNK cells in patients with URPL and uncovered a complicated crosstalk through the MAPK signal at the maternal-fetal interface.