Natural killer cell division regulates FcεRIγ expression downstream of mTOR activity

Abstract

AbstractThe expansion of human FcεRIγ-/low (FcRγ-/low) natural killer (NK) cells accrues during viral infections; however, the molecular mechanisms regulating FcRγ 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 FcRγ levels in the NK cell population. Moreover, lower FcRγ levels in healthy donors were associated with low mTORC1/C2 activity and low T-bet expression. Cell division suppression by rapamycin or TGFβ suppressed FcRγ upregulation during IL-2 receptor stimulation, whereas promoting NK cell division by co-inhibiting FOXO1 activity restored FcRγ upregulation. These results suggest that the human FcRγ-/low NK cell phenotype is associated with cell division suppression and reduced mTOR activity.