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 γt (RORγt) 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 RORγt 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.

Keywords: IL-22; NK cell; NK22 cell; RORγt; recurrent pregnancy loss.