Modulation of 17beta-estradiol on the number and cytotoxicity of NK cells in vivo related to MCM and activating receptors.

Natural killer (NK) cells are key components of immune systems and their activities could be regulated by sex hormones. In the present study we investigate the effects of estrogen on the number and cytotoxic activity of NK cells in vivo. The number and cytotoxicity of NK cells in four groups (control, sham+vehicle, Ovx+vehicle and Ovx+E2) were determined. The results showed that 17beta-estradiol (E2) increased the number of NK cells, but reduced their cytotoxicity. The increase of NK cells proportions by E2 may be mediated by up-regulating the expression of MCM7 and MCM10 proteins, which are required for DNA replication licensing in cell proliferation. The suppressed cytotoxicity of splenic NK cells by E2 may be attributable to the down-regulation of NK cells activating receptors-CD69, NKp46, NKG2DL and 2B4 (CD244), which directly inhibited NK cell activation, resulting in the reduced secretion of the soluble factors-granzyme B and FasL. INF-gamma might also act as a negative regulator in the low cytotoxicity of NK cells. In addition, the number of the NK cells is not parallel to their cytotoxicity with a long-term exposure to E2 in vivo. These results suggest that E2-mediated low cytotoxicity of NK cells may regulate host immune response in pregnancy and some female predominant diseases.