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Science. 2017 Sep 8;357(6355):1014-1021. doi: 10.1126/science.aaj2155. Epub 2017 Aug 10.

mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation.

Author information

1
Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
2
Department of Medicine, Emory University, Atlanta, GA 30329, USA.
3
Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
4
Yerkes Molecular Pathology Core Laboratory, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
5
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.
6
Primate Genomics Core, Yerkes National Primate Research Center, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
7
Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA. bpulend@emory.edu bpulend@stanford.edu.
8
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
9
Institute for Immunity, Transplantation and Infection, Department of Pathology, Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.

Abstract

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 (TH2) to neutrophilic TH17 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.

PMID:
28798047
PMCID:
PMC5746055
DOI:
10.1126/science.aaj2155
[Indexed for MEDLINE]
Free PMC Article

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