MTOR Regulates Metabolic Adaptation of APCs in the Lung and Controls the Outcome of Allergic Inflammation

Overview

Journal Science

Specialty Science

Date 2017 Aug 12

PMID 28798047

Citations 57

Authors

Charles Sinclair

Gayathri Bommakanti

Luiz Gardinassi

Jens Loebbermann

Matthew Joseph Johnson

Paul Hakimpour

Thomas Hagan

Lydia Benitez

Andrei Todor

Deepa Machiah

Timothy Oriss

Anuradha Ray

Steven Bosinger

Rajesh Ravindran

Shuzhao Li

Bali Pulendran

Affiliations

Soon will be listed here.

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 (T2) to neutrophilic T17 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.

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