Co-expression of activating and inhibitory receptors on peritoneal fluid NK cells in women with endometriosis

The detailed mechanism underlying endometriosis development remains unclear; few reports have suggested the involvement of immune and genetic factors. This study aims to investigate the role of NK cells in endometriosis by analyzing the co-expression of activating (NKp46, NKG2C, and NKG2D) and inhibitory receptors (NKG2A and CD158a) on NK cells and their subsequent cytokine production in the peritoneal fluid (PF). Sixty-two patients were enrolled for this study from Hyogo Medical University between February 2018 and April 2022. Results showed that the proportions of CD56+/NKp46+, CD56dim/NKp46+, NKG2C+/NKp46+, and NKG2D+/NKp46+ NK cells were significantly lower in the endometriosis group than those in the control group. Meanwhile, within the peritoneal endometriosis (n = 21) and deep infiltrating endometriosis (n = 11) groups, the co-expression of NKG2D+/NKp46+ and CD16+/NKp46+. Additionally, the abundance of IFN-gamma-producing NK cells was signifi-cantly increased in the endometriosis group compared to controls, and a significant negative correlation was noted between NKp46 expression on NK cells and type 1 cytokine (IFN-gamma and TNF-alpha) production. Taken together, the findings of this study indicate that NK cell cytotoxicity in endometriosis is reduced due to changes in NKp46 expression, as well as activating receptors co-expressed with NKp46. Consequently, NK cells do not eliminate endometrial cells in the abdominal cavity, resulting in the production of TNF-alpha and IFN-gamma.

Automated summary

This study investigates the role of NK cells in endometriosis and finds that the expression of activating receptors and inhibitory receptors on NK cells is decreased in endometriosis patients, while the production of TNF-alpha and IFN-gamma is increased. These findings suggest that the cytotoxic function of NK cells is inhibited in endometriosis, leading to the accumulation of endometrial cells in the abdominal cavity and the production of excessive TNF-alpha and IFN-gamma.