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

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

来源：Science, 2017, 357(6355): 1014-+.

DOI：10.1126/science.aaj2155

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.

• 出版日期2017-9-8