Journal
ELIFE
Volume 7, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.35619
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Funding
- National Institute of Allergy and Infectious Diseases
- National Cancer Institute
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI102893] Funding Source: NIH RePORTER
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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.
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