IL-25 promotes Th2 bias by upregulating IL-4 and IL-10 expression of decidual γδT cells in early pregnancy

Decidual immune cells (DICs), consisting of both innate and adaptive immune cells, have a pivotal role in maintaining immune tolerance for normal pregnancy. Our previous study demonstrated that interleukin (IL)-25 stimulates the proliferation of decidual stromal cells (DSCs) in an autocrine manner. However, the role of IL-25 in functional regulation of DICs is largely unknown. Flow cytometry was used to analyze the expression of IL-25 and its receptor (IL-17RB) in DICs, and the effect of IL-25 on the expression of Ki-67, IL-4, IL-10, interferon (IFN)-γ and transforming growth factor (TGF)-β in decidual γδT cells. In addition, ELISA assays were performed to detect the secretion of IL-10 and TGF-β in decidual γδT cells. The present findings indicated that decidual CD56 bright CD16-natural killer (NK) cells, natural killer T (NKT) cells, regulatory T (Treg) cells, CD3(+) T cells, macrophages and γδT cells co-expressed IL-25 and IL-17RB, particularly γδT cells. Recombinant human (rh) IL-25 protein upregulated the expression of Ki-67, IL-4, and IL-10, but downregulated the expression of IFN-γ in γδT cells; however, anti-human IL-25 or IL-17RB neutralizing antibody reversed these effects. These data suggest that IL-25 may promote IL-10 production by γδT cells as well as the proliferation of γδT cells, and possibly forms a positive feedback loop to maintain a T helper 2 cell bias at the maternal-fetal interface and further contributes to the maintenance of successful pregnancy.