Journal Article

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

Johnson, Matthew Joseph, Bosinger, Steven, Oriss, Timothy, Ravindran, Rajesh, Ray, Anuradha, Gardinassi, Luiz, Pulendran, Bali, Loebbermann, Jens, Todor, Andrei, Machiah, Deepa, Hakimpour, Paul, Bommakanti, Gayathri, Hagan, Thomas, Sinclair, Charles, Benitez, Lydia, Li, Shuzhao

2017

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Adaptation / Allergy / Alveoli / Animal models / Animals / Antigen Presentation / Antigen-presenting cells / Antigens / Antigens, CD - metabolism / CD103 antigen / CD11b antigen / CD11b Antigen - genetics / CD11b Antigen - metabolism / Dendritic cells / Dendritic Cells - immunology / Eosinophils - immunology / Fatty Acids - metabolism / Helper cells / Homeostasis / Hypersensitivity / Hypersensitivity - metabolism / Immune system / Immunology / Inflammation / Inflammation - metabolism / Integrin alpha Chains - metabolism / Interleukin 23 / Interleukin-23 - metabolism / Leukocytes (eosinophilic) / Leukocytes (neutrophilic) / Lung - metabolism / Lung - pathology / Lungs / Lymphocytes T / Lymphoid tissue / Macrophages / Metabolism / Mice / Mice, Inbred C57BL / Neutrophils - immunology / Organs / Oxidation / Oxidation-Reduction / Polarity / Rapamycin / Th17 Cells - immunology / Th2 Cells - immunology / Tissues / TOR protein / TOR Serine-Threonine Kinases - genetics / TOR Serine-Threonine Kinases - metabolism / Transcription