NK cells that differ in expression of NKp46 might play different roles in endometrium

Abstract

NKp46 is a natural cytotoxicity receptor expressed by NK cells and its expression is decreased in reproductive failure patients. NKp46 can be subdivided into NKp46^dim and NKp46^bright according to different fluorescence staining intensities. We investigated the role of the NKp46 receptor in determining the reproductive outcomes. Uterine endometrium was collected from 34 women with reproductive failure and divided into the pregnant and failed groups based on the results of a pregnancy reaction test during a 1-year follow-up period. NKp46 receptor and other activating or inhibitory receptors expressed on NK cells as well as intracellular cytokine production by NK cells were analyzed by multicolor flow cytometry. In the failed group, the percentage of NKp46^dim NK cells (P < 0.05) was significantly higher and percentages of NKp46^bright NK cells (P < 0.01) and CD16^-/CD56^bright NK cells (P < 0.05) were significantly lower than those in the pregnant group. NKp46^dim NK cells were significantly and positively correlated with CD16⁺/NKp46^dim NK cells; NKp46^bright NK cells were significantly and positively correlated with CD16^-/NKp46^bright NK cells. CD16⁺/NKp46^dim NK cells were significantly and positively correlated with IFN-γ- and/or TNF-α-producing NK cells; CD16^-/NKp46^bright NK cells were significantly and positively correlated with TGF-β1-producing NK cells. We suggest that the NKp46 receptor plays different roles in reproduction based on the different fluorescence intensities associated with NK cells, i.e. NKp46^dim NK cells are involved in killing cells, whereas NKp46^bright NK cells are involved in cytokine production, indicating that NKp46 could be a predictive marker to see a tolerate condition for embryos.

Keywords: IFN-γ; NK cell; NKp46; Recurrent pregnancy loss; Repeated implantation failure.