Expression of retinoid‐related orphan receptor (ROR)γt on NK22 cells in the peripheral blood and uterine endometrium of women with unexplained recurrent pregnancy loss and unexplained infertility

Abstract Aim Recently, NK22 cells, a subset of interleukin (IL)‐22‐producing natural killer (NK) cells, were identified. We have previously reported the higher percentage of NK22 cells in women suffering recurrent pregnancy loss (RPL). Moreover, we have also reported lower expression of NKp46, a kind of natural cytotoxicity receptor (NCR), on NK cells and the changes of NK cell producing cytokines in women who experience RPL. NK22 cells express NCRs, such as NKp44 or NKp46. Retinoid‐related orphan receptor γ t (ROR γ t) is known as a regulator of NK22 cells; however, in NK22 cells of peripheral blood (PB) and the uterine endometrium (UE), the relationship between NCRs and ROR γ t is unclear. We investigate RORγt expression NK22 cells in the PB and UE of women with unexplained infertility (uI) or unexplained RPL (uRPL). Methods Lymphocytes were extracted from PB and UE, derived from women with uI or uRPL. Expression of RORγt and NCRs in NK cells and NK cell‐produced cytokines were analyzed by flow cytometry. Results CD56 + /NKp46 + /RORγt + cells were positively correlated with CD56 + /IL‐22 + cells in both PB and UE. CD56 bright /NKp46 bright /RORγt + cells were significantly higher in uRPL than in uI, and endometrial CD56 bright /NKp46 bright /RORγt + cells were positively correlated with PB. In UE, CD56 bright /RORγt + cells were negatively correlated with CD56 bright /interferon‐γ + and CD56 bright /tumor necrosis factor‐α + cells of uRPL. Conclusion RORγt may be associated with NK22 cells in reproduction. Particularly, higher expression of RORγt may be associated with elevated NK22 cells in uRPL.