Faculty Collaboration Database

mTORC1 and mTORC2 differentially promote natural killer cell development. Elife 2018 May 29;7

Date

05/29/2018

Pubmed ID

29809146

Pubmed Central ID

PMC5976438

DOI

10.7554/eLife.35619

Scopus ID

2-s2.0-85051988950 (requires institutional sign-in at Scopus site)   49 Citations

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. 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.

Author List

Yang C, Tsaih SW, Lemke A, Flister MJ, Thakar MS, Malarkannan S

Authors

Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of Wisconsin
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Female
Killer Cells, Natural
Lung Neoplasms
Male
Mechanistic Target of Rapamycin Complex 1
Mechanistic Target of Rapamycin Complex 2
Melanoma, Experimental
Mice
Mice, Inbred C57BL
Mice, Knockout
Rapamycin-Insensitive Companion of mTOR Protein
Regulatory-Associated Protein of mTOR
Signal Transduction
T-Box Domain Proteins
Tumor Cells, Cultured