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

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-gamma- and/or TNF-alpha-producing NK cells; CD16(-)/NKp46(bright) NK cells were significantly and positively correlated with TGF-beta 1-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.