Natural Killer Cells Express Estrogen Receptor-α and Estrogen Receptor-β and Can Respond to Estrogen Via a Non-Estrogen Receptor-α-Mediated Pathway

Abstract

Natural killer (NK) cells play a crucial role in host defense against pathogens and immune surveillance against cancer. Given that estrogens have been reported to suppress NK cell activity, we sought to elucidate the mechanisms by which estrogen mediates this effect. We demonstrate by immunocytochemical staining with estrogen receptor-α (ERα)- and estrogen receptor-β (ERβ)-specific antibodies that both ERα and ERβ are expressed in murine NK cells. We also compared the ability of high doses of 17β-estradiol (∼800 pg/ml) to regulate NK cell activity in wild-type and estrogen receptor-α-deficient (ERαKO) mice. 17β-estradiol elicited a significant decrease in NK cell activity in both wild-type and ERαKO mice (P < 0.001). These data suggest that ERβ or possibly a novel receptor is involved in mediating estrogen action on NK cell activity and raise the potential for therapeutic modulation of NK cell activity with selective estrogen receptor modulators (SERMS).