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

ABSTRACT: Antigen presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working in mouse models of inflammation, we found that mTOR-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for DC homeostasis in secondary lymphoid tissues, but necessary to regulate cellular metabolism and accumulation of CD103+ DCs and alveolar macrophages in lung. Moreover, whilst numbers of mTOR-deficient lung CD11b+ DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic Th2 to neutrophilic Th17 polarity. The mechanism for this change was independent of translational control, but dependent on inflammatory DC which produced IL-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Sorted Cells

DISEASE(S): Inflammation

SUBMITTER: Shuzhao; Luiz Li; Gardinassi