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
Emory Vaccine Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
Department of Medicine, Emory University, Atlanta, GA 30329, USA.
Science. 2017 Sep 8;357(6355):1014-1021. doi: 10.1126/science.aaj2155. Epub 2017 Aug 10.
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.
抗原呈递细胞（APC）存在于多种解剖组织中，但其组织限制性稳态仍知之甚少。在这里，我们利用炎症小鼠模型发现，在不同位置需要雷帕霉素的机制性靶点（mTOR）依赖性代谢适应。mTOR对于次级淋巴组织中树突状细胞（DC）的稳态是可有可无的，但对于调节肺中CD103 DC和肺泡巨噬细胞的细胞代谢和积累是必需的。此外，虽然mTOR缺陷型肺CD11b DC的数量没有变化，但它们在代谢上被重新编程，使过敏性炎症从嗜酸性辅助性T细胞2（T2）偏向嗜中性T17极性。这种变化的机制独立于翻译控制，但依赖于产生白细胞介素-23并增加脂肪酸氧化的炎性DC。因此，mTOR介导不同组织中APC的代谢适应，影响过敏性炎症的免疫学特征。
