Natural Killer Cells: Key Players in Endometriosis

Abstract

Endometriosis affects more than 10% of women, causing significant pain and morbidity. It is also a significant cause of infertility. The aetiology of the disease remains an enigma, and the mechanisms responsible for the associated infertility are unclear. A role for immune cells in endometriosis has been postulated, with attention directed towards natural killer (NK) cells and macrophages. NK cells kill tumours and infected cells but also have roles in tissue remodelling in several organs including the uterus and are key to successful pregnancy. Here, we explore evidence (from peer-reviewed published articles) of phenotypic and functional abnormalities in NK cell subpopulations of women with endometriosis. It is clear that peripheral blood NK cells and peritoneal NK cells have reduced cytotoxic function in women with endometriosis. Uterine NK cells have a vital role in infertility, but very little research has been carried out in this area. We propose that abnormal u NK cell activity may contribute to the pathogenesis of endometriosis and its associated infertility and that future research should focus on this complex area.

Immune-inflammation gene signatures in endometriosis patients

“…Consequently, decreased expression of both SIGIRR and CEACAM-1 genes in ectopic tissues may explain the dysregulated inflammatory cytokine elevation and T-cell activation observed in endometriosis patients. Furthermore, decreased expression of NFIL3 (32), IL15 (33), and GNLY (34) in ectopic lesions support diminished cytotoxicity of NK and CD8+ T cells in women with endometriosis toward autologous endometrial fragments (35, 36). The expression of genes involved in signaling pathways, including TRAF4, MAPK1 , and DUSP4 , were significantly decreased in expression in ectopic tissues compared with control endometrium.…”

Involvement of immune cells in the pathogenesis of endometriosis

“…With regard to endometriosis, the cytotoxic function is reduced in peripheral and peritoneal NK cells. [53][54][55][56][57] Due to diminished cytotoxicity, retrograde endometrial cells are prone to survive in the peritoneal cavity, which results in the development of endometriosis. Factors controlling NK cell function have not been thoroughly investigated; however, several studies have shown that IL-6, 57 IL-15, 58 and transforming growth factor-β1 59 suppress NK cell cytotoxic activity.…”

“…With regard to endometriosis, the cytotoxic function is reduced in peripheral and peritoneal NK cells . Due to diminished cytotoxicity, retrograde endometrial cells are prone to survive in the peritoneal cavity, which results in the development of endometriosis.…”

Bioinformatics strategy for the screening of key genes to differentiate adenomyosis from endometriosis (Review)

“…NK cells have a decreased expression of inhibitory KIRs, including KIR3DL1 (also known as NKB1) and KIR2DL3 (also known as GL183), on their surface and have enhanced cytotoxic functions. In endometriosis, peripheral NK cells and peritoneal NK cells exhibit an increased expression of KIRs and have reduced levels of cytotoxicity (63). Endometriotic cells develop several strategies to escape immune surveillance to avoid attack from the immune system.…”