mTORC1 and mTORC2 differentially promote natural killer cell development

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Abstract

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. Ncr1iCre-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-AktS473-FoxO1 signaling. Collectively, our results reveal the divergent roles of mTORC1 and mTORC2 in NK cell development.

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Yang, C., Tsaih, S. W., Lemke, A., Flister, M. J., Thakar, M. S., & Malarkannan, S. (2018). mTORC1 and mTORC2 differentially promote natural killer cell development. ELife, 7. https://doi.org/10.7554/eLife.35619

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