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

Abstract

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⁺, CD56^dim/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-γ-producing NK cells was significantly 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-γ and TNF-α) 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-α and IFN-γ.

Keywords: Endometriosis; IFN-γ; NKG2D; NKp46; Natural killer cell.