PMID- 29809146
OWN - NLM
STAT- MEDLINE
DCOM- 20190424
LR  - 20200313
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 7
DP  - 2018 May 29
TI  - mTORC1 and mTORC2 differentially promote natural killer cell development.
LID - 10.7554/eLife.35619 [doi]
LID - e35619
AB  - 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.
CI  - (c) 2018, Yang et al.
FAU - Yang, Chao
AU  - Yang C
AD  - Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, 
      Blood Center of Wisconsin, Milwaukee, United States.
AD  - Departments of Microbiology and Immunology, Medical College of Wisconsin, 
      Milwaukee, United States.
FAU - Tsaih, Shirng-Wern
AU  - Tsaih SW
AD  - Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, 
      United States.
AD  - Departments of Physiology, Medical College of Wisconsin, Milwaukee, United 
      States.
FAU - Lemke, Angela
AU  - Lemke A
AD  - Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, 
      United States.
AD  - Departments of Physiology, Medical College of Wisconsin, Milwaukee, United 
      States.
FAU - Flister, Michael J
AU  - Flister MJ
AD  - Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, 
      United States.
AD  - Departments of Physiology, Medical College of Wisconsin, Milwaukee, United 
      States.
FAU - Thakar, Monica S
AU  - Thakar MS
AD  - Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, 
      Blood Center of Wisconsin, Milwaukee, United States.
AD  - Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, United 
      States.
FAU - Malarkannan, Subramaniam
AU  - Malarkannan S
AUID- ORCID: 0000-0002-7511-2731
AD  - Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, 
      Blood Center of Wisconsin, Milwaukee, United States.
AD  - Departments of Microbiology and Immunology, Medical College of Wisconsin, 
      Milwaukee, United States.
AD  - Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, United 
      States.
AD  - Departments of Medicine, Medical College of Wisconsin, Milwaukee, United States.
LA  - eng
GR  - R01 AI102893/AI/NIAID NIH HHS/United States
GR  - R01 CA179363/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180529
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (Regulatory-Associated Protein of mTOR)
RN  - 0 (Rptor protein, mouse)
RN  - 0 (T-Box Domain Proteins)
RN  - 0 (T-box transcription factor TBX21)
RN  - 0 (rictor protein, mouse)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
SB  - IM
MH  - Animals
MH  - Female
MH  - Killer Cells, Natural/*cytology/immunology/metabolism
MH  - Lung Neoplasms/immunology/metabolism/secondary
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1/genetics/*metabolism
MH  - Mechanistic Target of Rapamycin Complex 2/genetics/*metabolism
MH  - Melanoma, Experimental/immunology/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Rapamycin-Insensitive Companion of mTOR Protein/physiology
MH  - Regulatory-Associated Protein of mTOR/physiology
MH  - Signal Transduction
MH  - T-Box Domain Proteins/genetics/*metabolism
MH  - Tumor Cells, Cultured
PMC - PMC5976438
OTO - NOTNLM
OT  - NK cells
OT  - Raptor
OT  - Rictor
OT  - immunology
OT  - inflammation
OT  - mouse
COIS- CY, ST, AL, MF, MT, SM No competing interests declared
EDAT- 2018/05/29 06:00
MHDA- 2019/04/25 06:00
PMCR- 2018/05/29
CRDT- 2018/05/30 06:00
PHST- 2018/02/01 00:00 [received]
PHST- 2018/05/13 00:00 [accepted]
PHST- 2018/05/29 06:00 [pubmed]
PHST- 2019/04/25 06:00 [medline]
PHST- 2018/05/30 06:00 [entrez]
PHST- 2018/05/29 00:00 [pmc-release]
AID - 35619 [pii]
AID - 10.7554/eLife.35619 [doi]
PST - epublish
SO  - Elife. 2018 May 29;7:e35619. doi: 10.7554/eLife.35619.