Mechanisms of the Effect of Simulated Microgravity on the Cytotoxicity of NK Cells Following the DNA Methylation of NKG2D and the Expression of DAP10

Abstract

The inhibition of the cytotoxicity of NK cells by microgravity in space is of serious concern to the health of astronauts. However, there remains a lack of in-depth research into the mechanisms of action of this suppression. In the present study, the effects of simulated microgravity (SMG) on the morphology, survival rate and the ability of NK cells to kill were studied initially and then the mechanism of SMG in the inhibition of NK cytotoxicity was preliminarily investigated from the perspectives of stimulatory and inhibitory receptor expression. Further, the present study attempted to reveal the molecular mechanisms of SMG inhibition of the stimulatory receptor NKG2D from the perspective of DNA methylation and the expression of its adaptor protein DAP10. The results demonstrated that down-regulation of stimulatory receptor NKG2D expression and significantly up-regulated expression of inhibitory receptor CD158a may be important in explaining for the inhibition of NK cell cytotoxicity by SMG. The down-regulation of DAP10 expression, and not its DNA methylation, that is the possible cause of the down-regulation of NKG2D expression by SMG and the subsequent suppression of NK cell activity. However, inhibition of DAP10 expression by SMG was also not achieved by influencing methylation, and so additional analysis of the mechanism is required. The results of the present study lay the foundations for finally elucidating the molecular mechanisms by which microgravity leads to a decline in NK cell activity and contributes important evidence for interpreting the regulatory mechanisms of NK cell cytotoxicity.