mTORC1 and mTORC2 differentially promote natural killer cell development
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. -mediated deletion of or...
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Published in | eLife Vol. 7 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
England
eLife Sciences Publications Ltd
29.05.2018
eLife Sciences Publications, Ltd |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
-mediated deletion of
or
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
cKO mice, while, the terminal maturation from the CD27
CD11b
to the CD27
CD11b
stage is compromised in
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
-FoxO1 signaling. Collectively, our results reveal the divergent roles of mTORC1 and mTORC2 in NK cell development. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2050-084X 2050-084X |
DOI: | 10.7554/elife.35619 |