Natural Killer cell division regulates FcεRIγ expression downstream of mTOR activity

The expansion of human Fc{varepsilon}RI{gamma}-/low (FcR{gamma}-/low) natural killer (NK) cells accrues during viral infections; however, the molecular mechanisms regulating FcR{gamma} expression is not well defined and can have implication for host protection and NK cell immunotherapy. Our analysis of NK cell subsets in lung transplant patients during rapamycin treatment revealed significantly lower FcR{gamma} levels in the NK cell population. Moreover, lower FcR{gamma} levels in healthy donors were associated with low mTORC1/C2 activity and low T-bet expression. Cell division suppression by rapamycin or TGF{beta} suppressed FcR{gamma} upregulation during IL-2 receptor stimulation, whereas promoting NK cell division by co-inhibiting FOXO1 activity restored FcR{gamma} upregulation. These results suggest that the human FcR{gamma}-/low NK cell phenotype is associated with cell division suppression and reduced mTOR activity.