IL-22 secreted by decidual stromal cells and NK cells promotes the survival of human trophoblasts

Interleukin-22 (IL-22) has been implicated as an important immune regulator in many physiologic and pathological processes, but little is known about the IL-22 in the fetal-maternal interface. In this study, we demonstrated that co-culture of decidual stromal cells (DSCs) and decidual natural killer (dNK) cells resulted in increased secretion of IL-22, compared to culture of DSCs or dNK cells alone. The trophoblast cell line, HTR8/SVneo, expresses IL-22 receptor α1 (IL-22R1). Combinant human (rh) IL-22 significantly promoted the proliferation and viability, and inhibited the apoptosis of HTR8/SVneo cells. By Western blotting and immunohistochemistry, we confirmed that villi expressed IL-22R1, and the villi from unexplained spontaneous miscarriage patients expressed reduced levels of IL-22R1 than those from normal early pregnancy. These findings indicate that the IL-22 secreted by DSCs and dNK might promote the survival of trophoblasts and participate in the maintenance of pregnancy by binding to the IL-22R1. The reduced level of IL-22/IL-22R1 in villi might be involved in the occurrence of spontaneous miscarriage.