PMID- 25108022
OWN - NLM
STAT- MEDLINE
DCOM- 20141125
LR  - 20211203
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 193
IP  - 6
DP  - 2014 Sep 15
TI  - Mechanistic target of rapamycin inhibition extends cellular lifespan in dendritic 
      cells by preserving mitochondrial function.
PG  - 2821-30
LID - 10.4049/jimmunol.1302498 [doi]
AB  - TLR-mediated activation of dendritic cells (DCs) is associated with a metabolic 
      transition in which mitochondrial oxidative phosphorylation is inhibited by 
      endogenously synthesized NO and the cells become committed to glucose and aerobic 
      glycolysis for survival. We show that inhibition of mechanistic target of 
      rapamycin (mTOR) extends the lifespan of TLR-activated DCs by inhibiting the 
      induction of NO production, thereby allowing the cells to continue to use their 
      mitochondria to generate ATP, and allowing them the flexibility to use fatty 
      acids or glucose as nutrients to fuel core metabolism. These data provide novel 
      mechanistic insights into how mTOR modulates DC metabolism and cellular longevity 
      following TLR activation and provide an explanation for previous findings that 
      mTOR inhibition enhances the efficacy of DCs in autologous vaccination.
CI  - Copyright (c) 2014 by The American Association of Immunologists, Inc.
FAU - Amiel, Eyal
AU  - Amiel E
AD  - Department of Medical Laboratory and Radiation Sciences, College of Nursing and 
      Health Sciences, University of Vermont, Burlington, VT 05405; Trudeau Institute, 
      Saranac Lake, NY 12983; and.
FAU - Everts, Bart
AU  - Everts B
AD  - Department of Pathology and Immunology, Washington University School of Medicine, 
      St. Louis, MO 63110.
FAU - Fritz, Daniel
AU  - Fritz D
AD  - Department of Medical Laboratory and Radiation Sciences, College of Nursing and 
      Health Sciences, University of Vermont, Burlington, VT 05405;
FAU - Beauchamp, Saritha
AU  - Beauchamp S
AD  - Department of Medical Laboratory and Radiation Sciences, College of Nursing and 
      Health Sciences, University of Vermont, Burlington, VT 05405;
FAU - Ge, Burong
AU  - Ge B
AD  - Department of Medical Laboratory and Radiation Sciences, College of Nursing and 
      Health Sciences, University of Vermont, Burlington, VT 05405;
FAU - Pearce, Erika L
AU  - Pearce EL
AD  - Department of Pathology and Immunology, Washington University School of Medicine, 
      St. Louis, MO 63110.
FAU - Pearce, Edward J
AU  - Pearce EJ
AD  - Department of Pathology and Immunology, Washington University School of Medicine, 
      St. Louis, MO 63110 edwardpearce@path.wustl.edu.
LA  - eng
GR  - CA155823/CA/NCI NIH HHS/United States
GR  - AI049823/AI/NIAID NIH HHS/United States
GR  - AI 091965/AI/NIAID NIH HHS/United States
GR  - R01 CA164062/CA/NCI NIH HHS/United States
GR  - R21 CA155823/CA/NCI NIH HHS/United States
GR  - T32 AI049823/AI/NIAID NIH HHS/United States
GR  - R01 AI091965/AI/NIAID NIH HHS/United States
GR  - AI053825/AI/NIAID NIH HHS/United States
GR  - R21 CA158823/CA/NCI NIH HHS/United States
GR  - P20 GM103496/GM/NIGMS NIH HHS/United States
GR  - R01 AI053825/AI/NIAID NIH HHS/United States
GR  - CA164062/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140808
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Fatty Acids)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Toll-Like Receptors)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adenosine Triphosphate/biosynthesis
MH  - Animals
MH  - Cells, Cultured
MH  - Cellular Senescence/immunology
MH  - Dendritic Cells/immunology/*metabolism
MH  - Fatty Acids/metabolism
MH  - Glucose/metabolism
MH  - Glycolysis
MH  - Lipopolysaccharides
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria/*metabolism
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/biosynthesis/genetics/*metabolism
MH  - Oxidative Phosphorylation
MH  - Protein Biosynthesis
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Toll-Like Receptors/*immunology
MH  - Transcription, Genetic
MH  - Vaccination
PMC - PMC4302759
MID - NIHMS654149
EDAT- 2014/08/12 06:00
MHDA- 2014/12/15 06:00
PMCR- 2015/03/15
CRDT- 2014/08/10 06:00
PHST- 2014/08/10 06:00 [entrez]
PHST- 2014/08/12 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2015/03/15 00:00 [pmc-release]
AID - jimmunol.1302498 [pii]
AID - 10.4049/jimmunol.1302498 [doi]
PST - ppublish
SO  - J Immunol. 2014 Sep 15;193(6):2821-30. doi: 10.4049/jimmunol.1302498. Epub 2014 
      Aug 8.