PMID- 28798047
OWN - NLM
STAT- MEDLINE
DCOM- 20180306
LR  - 20211204
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 357
IP  - 6355
DP  - 2017 Sep 8
TI  - mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome 
      of allergic inflammation.
PG  - 1014-1021
LID - 10.1126/science.aaj2155 [doi]
AB  - Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their 
      tissue-restricted homeostasis remains poorly understood. Here, working with mouse 
      models of inflammation, we found that mechanistic target of rapamycin 
      (mTOR)-dependent metabolic adaptation was required at discrete locations. mTOR 
      was dispensable for dendritic cell (DC) homeostasis in secondary lymphoid tissues 
      but necessary to regulate cellular metabolism and accumulation of CD103(+) DCs 
      and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung 
      CD11b(+) DCs were not changed, they were metabolically reprogrammed to skew 
      allergic inflammation from eosinophilic T helper cell 2 (T(H)2) to neutrophilic 
      T(H)17 polarity. The mechanism for this change was independent of translational 
      control but dependent on inflammatory DCs, which produced interleukin-23 and 
      increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of 
      APCs in distinct tissues, influencing the immunological character of allergic 
      inflammation.
CI  - Copyright (c) 2017 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Sinclair, Charles
AU  - Sinclair C
AUID- ORCID: 0000-0001-6857-9993
AD  - Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, 
      USA.
FAU - Bommakanti, Gayathri
AU  - Bommakanti G
AUID- ORCID: 0000-0002-3420-2802
AD  - Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, 
      USA.
FAU - Gardinassi, Luiz
AU  - Gardinassi L
AUID- ORCID: 0000-0002-9027-2688
AD  - Department of Medicine, Emory University, Atlanta, GA 30329, USA.
FAU - Loebbermann, Jens
AU  - Loebbermann J
AUID- ORCID: 0000-0003-1439-0073
AD  - Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, 
      USA.
FAU - Johnson, Matthew Joseph
AU  - Johnson MJ
AUID- ORCID: 0000-0002-1313-1742
AD  - Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, 
      USA.
AD  - Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
FAU - Hakimpour, Paul
AU  - Hakimpour P
AD  - Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, 
      USA.
FAU - Hagan, Thomas
AU  - Hagan T
AUID- ORCID: 0000-0002-5254-5251
AD  - Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, 
      USA.
FAU - Benitez, Lydia
AU  - Benitez L
AD  - Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, 
      USA.
FAU - Todor, Andrei
AU  - Todor A
AD  - Department of Medicine, Emory University, Atlanta, GA 30329, USA.
FAU - Machiah, Deepa
AU  - Machiah D
AD  - Yerkes Molecular Pathology Core Laboratory, Yerkes National Primate Research 
      Center, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
FAU - Oriss, Timothy
AU  - Oriss T
AUID- ORCID: 0000-0002-9725-9996
AD  - Division of Pulmonary, Allergy and Critical Care Medicine, Department of 
      Immunology, University of Pittsburgh Asthma Institute at University of Pittsburgh 
      Medical Center (UPMC), University of Pittsburgh School of Medicine, Pittsburgh, 
      PA, USA.
FAU - Ray, Anuradha
AU  - Ray A
AD  - Division of Pulmonary, Allergy and Critical Care Medicine, Department of 
      Immunology, University of Pittsburgh Asthma Institute at University of Pittsburgh 
      Medical Center (UPMC), University of Pittsburgh School of Medicine, Pittsburgh, 
      PA, USA.
FAU - Bosinger, Steven
AU  - Bosinger S
AD  - Primate Genomics Core, Yerkes National Primate Research Center, 954 Gatewood Road 
      NE, Atlanta, GA 30329, USA.
FAU - Ravindran, Rajesh
AU  - Ravindran R
AUID- ORCID: 0000-0002-1357-2564
AD  - Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, 
      USA.
FAU - Li, Shuzhao
AU  - Li S
AD  - Department of Medicine, Emory University, Atlanta, GA 30329, USA.
FAU - Pulendran, Bali
AU  - Pulendran B
AUID- ORCID: 0000-0001-6517-4333
AD  - Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, 
      USA. bpulend@emory.edu bpulend@stanford.edu.
AD  - Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, 
      USA.
AD  - Institute for Immunity, Transplantation and Infection, Department of Pathology, 
      Department of Microbiology and Immunology, Stanford University, Stanford, CA 
      94305, USA.
LA  - eng
GR  - R37 AI048638/AI/NIAID NIH HHS/United States
GR  - U19 AI090023/AI/NIAID NIH HHS/United States
GR  - P51 OD011132/OD/NIH HHS/United States
GR  - U19 AI057266/AI/NIAID NIH HHS/United States
GR  - R37 DK057665/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170810
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Antigens, CD)
RN  - 0 (CD11b Antigen)
RN  - 0 (Fatty Acids)
RN  - 0 (Integrin alpha Chains)
RN  - 0 (Interleukin-23)
RN  - 0 (alpha E integrins)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - Science. 2017 Sep 8;357(6355):973-974. PMID: 28883060
MH  - Animals
MH  - Antigen Presentation
MH  - Antigens, CD/metabolism
MH  - CD11b Antigen/genetics/metabolism
MH  - Dendritic Cells/*immunology
MH  - Eosinophils/immunology
MH  - Fatty Acids/metabolism
MH  - *Homeostasis
MH  - Hypersensitivity/*metabolism
MH  - Inflammation/*metabolism
MH  - Integrin alpha Chains/metabolism
MH  - Interleukin-23/metabolism
MH  - Lung/*metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neutrophils/immunology
MH  - Oxidation-Reduction
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Th17 Cells/immunology
MH  - Th2 Cells/immunology
PMC - PMC5746055
MID - NIHMS929362
EDAT- 2017/08/12 06:00
MHDA- 2018/03/07 06:00
PMCR- 2018/09/08
CRDT- 2017/08/12 06:00
PHST- 2016/09/14 00:00 [received]
PHST- 2017/03/29 00:00 [revised]
PHST- 2017/06/22 00:00 [accepted]
PHST- 2017/08/12 06:00 [pubmed]
PHST- 2018/03/07 06:00 [medline]
PHST- 2017/08/12 06:00 [entrez]
PHST- 2018/09/08 00:00 [pmc-release]
AID - science.aaj2155 [pii]
AID - 10.1126/science.aaj2155 [doi]
PST - ppublish
SO  - Science. 2017 Sep 8;357(6355):1014-1021. doi: 10.1126/science.aaj2155. Epub 2017 
      Aug 10.