Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation.
Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation.
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DOI：
10.1038/ni.3421
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发表时间：
2016-06
影响因子：
30.5
通讯作者：
Artis D
中科院分区：
文献类型：
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作者：
Monticelli LA;Buck MD;Flamar AL;Saenz SA;Tait Wojno ED;Yudanin NA;Osborne LC;Hepworth MR;Tran SV;Rodewald HR;Shah H;Cross JR;Diamond JM;Cantu E;Christie JD;Pearce EL;Artis D
2组先天淋巴样细胞（ILC2s）在细胞外源因子（包括宿主源性细胞因子）激活后调节组织炎症和修复。然而，控制ILC2功能的细胞内在代谢途径尚不明确。在这里，我们证明了精氨酸酶1 （Arg1）的表达是小鼠和人类ILC2s在急性或慢性肺部炎症期间的一个保守特征。小鼠ilc -内在Arg1的缺失通过抑制ILC2增殖和抑制细胞因子的产生来消除2型肺炎症。从机制上讲，抑制Arg1酶活性通过改变精氨酸分解代谢、损害多胺生物合成和减少有氧糖酵解来破坏ILC2代谢程序的多个组成部分。这些数据表明Arg1是ILC2生物能量学的关键调节因子，控制增殖能力和促进2型炎症的促炎功能。
Group 2 innate lymphoid cells (ILC2s) regulate tissue inflammation and repair following activation by cell-extrinsic factors including host-derived cytokines. However, the cell-intrinsic metabolic pathways that control ILC2 function are undefined. Here we demonstrate that expression of the enzyme Arginase 1 (Arg1) is a conserved trait of murine and human ILC2s during acute or chronic lung inflammation. Deletion of murine ILC-intrinsic Arg1 abrogated type 2 lung inflammation by restraining ILC2 proliferation and dampening cytokine production. Mechanistically, inhibition of Arg1 enzymatic activity disrupted multiple components of ILC2 metabolic programming by altering arginine catabolism, impairing polyamine biosynthesis and reducing aerobic glycolysis. These data identify Arg1 as a key regulator of ILC2 bioenergetics, controlling proliferative capacity and pro-inflammatory functions that promote type 2 inflammation.