Uterine natural killer cells (uNK) do not express progesterone receptor, but express glucocorticoid receptor (GR). So, we speculate that progesterone may regulate uNK cells through a GR‐mediated process.

After mouse NK cells were stimulated with CpG with or without IL‐12 in the presence or absence pre‐treatment of progesterone, the effects of progesterone on NK via GR were investigated by using RU486 (progesterone receptor and GR antagonist) and CDB‐2914 (progesterone receptor antagonist). The expressions of CD69 and IFN‐γ were determined by flow cytometry and qPCR. Phosphorylation of IκB and STAT4 was determined by Western blot. Furthermore, we purified uNK cells from human decidual tissues using anti‐CD56 microbeads to verify the effect of progesterone on uNK via GR.

Progesterone suppressed CD69 and IFN‐γ expression of mouse spleen NK cells and human uNK cells induced by CpG combined with IL‐12. CDB‐2914 had no effect on IFN‐γ expression suppressed by progesterone, while RU486 could abolish the inhibitory effect of progesterone. In addition, progesterone could decrease the phosphorylation of both STAT4 and IκB.

In the present study, we first prove that progesterone can regulate NK cells via GR. It is valuable for further understanding the role of uNK in progesterone regulated gestation process.