| First Author | Yang C | Year | 2018 |
| Journal | Elife | Volume | 7 |
| PubMed ID | 29809146 | Mgi Jnum | J:264200 |
| Mgi Id | MGI:6191872 | Doi | 10.7554/eLife.35619 |
| Citation | Yang C, et al. (2018) mTORC1 and mTORC2 differentially promote natural killer cell development. Elife 7:e35619 |
| abstractText | Natural killer (NK) cells are innate lymphoid cells that are essential for innate and adaptive immunity. Mechanistic target of rapamycin (mTOR) is critical for NK cell development; however, the independent roles of mTORC1 or mTORC2 in regulating this process remain unknown. Ncr1(iCre)-mediated deletion of Rptor or Rictor in mice results in altered homeostatic NK cellularity and impaired development at distinct stages. The transition from the CD27(+)CD11b(-) to the CD27(+)CD11b(+) stage is impaired in Rptor cKO mice, while, the terminal maturation from the CD27(+)CD11b(+) to the CD27(-)CD11b(+) stage is compromised in Rictor cKO mice. Mechanistically, Raptor-deficiency renders substantial alteration of the gene expression profile including transcription factors governing early NK cell development. Comparatively, loss of Rictor causes more restricted transcriptome changes. The reduced expression of T-bet correlates with the terminal maturation defects and results from impaired mTORC2-Akt(S473)-FoxO1 signaling. Collectively, our results reveal the divergent roles of mTORC1 and mTORC2 in NK cell development. |
