Signaling By The Kinase MTOR Complexes,mTORC1 And MTORC2,Differentially Regulates NK Cell Development,Cytotoxicity And Cytokine Production

mTOR is indispensable for NK cells maturation,homeostasis and function.However,the effect of mTOR complex on the development,homeostasis and function of NK cells remain elusive.Here,we reveal that mTOR,mainly through mTORC1,is required for early NK cells development and terminal stage of NK cells maturation and homeostasis.NK cell progenitor stage-specific deletion of mTOR or Raptor,a component of mTORC1,largely reduce the expression of CD122,E4BP4,Eomes and T-bet,implying mTORC1 is essential for the process of NK cells.Raptor-null NK cells display more serious reduction of cytokine production,degranulation and conjugate formation than mTOR-deficient NK cells,whereas Rictor deletion is comparable with wild type.By using the combination of different genetic knockout model,we prove that mTORC2 play an inhibitory role when mTORC1 deficiency on this process.These results reveal a role for mTOR complexes differently regulate NK cells development,cytotoxicity and cytokine production.