Co-expression of NKp46 with activating or inhibitory receptors on, and cytokine production by, uterine endometrial NK cells in recurrent pregnancy loss

Abstract

NKp46 (CD335) is one of the activating receptors expressed on NK cells and its expression is decreased in patients with reproductive failure. However, the reasons remain unknown. In this study, we aimed to clarify the significance of decreased NKp46 expression in reproductive failure. Uterine endometrial samples collected from 39 patients with recurrent pregnancy loss (RPL) were assigned to high- or low-risk groups based on an 18 % ratio of CD16⁺/CD56^dim NK cells in uterine endometrial NK (uNK) cells. We analyzed the expression of NKp46 and other activating or inhibitory receptors on, and intracellular cytokine production by NK cells using multicolor flow cytometry. The numbers of NKp46⁺/CD16^- NK, NKp46⁺/NKG2C^- NK, IL-4⁺/CD56⁺ NK, and IL-10⁺/CD56⁺ NK cells were significantly decreased, whereas that TNF-α⁺/CD56⁺ NK cells was significantly increased in the high-risk group, when compared with the low-risk group (P < 0.05 for all). The ratios of TNF-α/IL-4, IFN-γ/IL4, TNF-α/IL-10, and IFN-γ/IL10 cytokine production in uNK cells were significantly increased in the high-risk when compared with the low-risk group (P < 0.05, for all). It is suggested that low expression of activating receptors on NKp46 uNK cells is more prevalent in high-risk women.

Keywords: Activating receptor; Cytokine; NKp46; Pregnancy; Uterine NK cell.