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mTORC1 and mTORC2 differentially promote natural killer cell development

Yang, Chao, Tsaih, Shirng-Wern, Lemke, Angela, Flister, Michael J, Thakar, Monica S, Malarkannan, Subramaniam·2018·eLife
DOI 10.7554/elife.35619PMC PMC5976438
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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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Metadata

Authors
Yang, C., Tsaih, S.-W., Lemke, A., Flister, M. J., Thakar, M. S., & Malarkannan, S.
Affiliations
  • Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Blood Center of Wisconsin, Milwaukee, United States
  • Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, United States
ORCID
Malarkannan, Subramaniam
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2018-05-29
Volume
7
ISSN
2050-084X
DOI
10.7554/elife.35619
PMC
PMC5976438
Cited by
77
References
6
Language
en
Licence
Funders
  • National Institute of Allergy and Infectious Diseases
  • National Cancer Institute

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