Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation

Monticelli Laurel A.; Buck Michael D.; Flamar Anne-Laure; Saenz Steven A.; Wojno Elia D. Tait; Yudanin Naomi A.; Osborne Lisa C.; Hepworth Matthew R.; Tran Sara V.; Rodewald Hans-Reimer; Shah Hardik; Cross Justin R.; Diamond Joshua M.; Cantu Edward; Christie Jason D.; Pearce Erika L.; Artis David

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Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation

机译：氨基酶1是一种先天淋巴细胞内在代谢检查点控制2型炎症

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Group 2 innate lymphoid cells (ILC2s) regulate tissue inflammation and repair after activation by cell-extrinsic factors such as 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) during acute or chronic lung inflammation is a conserved trait of mouse and human ILC2s. Deletion of mouse 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 that controls proliferative capacity and proinflammatory functions promoting type 2 inflammation.

机译：第2组先天淋巴细胞（ILC2S）通过细胞外部因子（如宿主衍生的细胞因子）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未定义。在这里，我们证明酶氨基酶-1（Arg1）在急性或慢性肺炎期间表达是小鼠和人ILC2s的保守特征。通过抑制ILC2增殖和抑制细胞因子产生，缺失小鼠ILC内在ARG1废除2型肺炎。机械地，通过改变精氨酸分解代谢，损害多胺生物合成和减少需氧糖酵解，抑制ArC1酶活性的抑制破坏了ILC2代谢编程的多种组分。这些数据鉴定ARG1作为ILC2生物植物的关键调节器，其控制增殖能力和促进型炎症的增殖能力和促炎功能。

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《Nature immunology》 |2016年第6期|共12页
作者
Monticelli Laurel A.; Buck Michael D.; Flamar Anne-Laure; Saenz Steven A.; Wojno Elia D. Tait; Yudanin Naomi A.; Osborne Lisa C.; Hepworth Matthew R.; Tran Sara V.; Rodewald Hans-Reimer; Shah Hardik; Cross Justin R.; Diamond Joshua M.; Cantu Edward; Christie Jason D.; Pearce Erika L.; Artis David;
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作者单位

Cornell Univ Joan &

Sanford I Weill Dept Med Jill Roberts Inst Res Inflammatory Bowel Dis Dept;

Max Plank Inst Immunobiol &

Epigenet Dept Immunometab Freiburg Germany;

Cornell Univ Joan &

Sanford I Weill Dept Med Jill Roberts Inst Res Inflammatory Bowel Dis Dept;

Cornell Univ Joan &

Sanford I Weill Dept Med Jill Roberts Inst Res Inflammatory Bowel Dis Dept;

Cornell Univ Joan &

Sanford I Weill Dept Med Jill Roberts Inst Res Inflammatory Bowel Dis Dept;

Cornell Univ Joan &

Sanford I Weill Dept Med Jill Roberts Inst Res Inflammatory Bowel Dis Dept;

Cornell Univ Joan &

Sanford I Weill Dept Med Jill Roberts Inst Res Inflammatory Bowel Dis Dept;

Cornell Univ Joan &

Sanford I Weill Dept Med Jill Roberts Inst Res Inflammatory Bowel Dis Dept;

Cornell Univ Joan &

Sanford I Weill Dept Med Jill Roberts Inst Res Inflammatory Bowel Dis Dept;

German Canc Res Ctr Div Cellular Immunol Heidelberg Germany;

Mem Sloan Kettering Canc Ctr Donald B &

Catherine C Marron Canc Metab Ctr 1275 York Ave New York;

Mem Sloan Kettering Canc Ctr Donald B &

Catherine C Marron Canc Metab Ctr 1275 York Ave New York;

Univ Penn Perelman Sch Med Ctr Translat Lung Biol Div Cardiovasc Surg Philadelphia PA 19104 USA;

Univ Penn Perelman Sch Med Ctr Translat Lung Biol Div Cardiovasc Surg Philadelphia PA 19104 USA;

Univ Penn Perelman Sch Med Ctr Translat Lung Biol Div Cardiovasc Surg Philadelphia PA 19104 USA;

Max Plank Inst Immunobiol &

Epigenet Dept Immunometab Freiburg Germany;

Cornell Univ Joan &

Sanford I Weill Dept Med Jill Roberts Inst Res Inflammatory Bowel Dis Dept;

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正文语种 eng
中图分类医学免疫学;
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1. Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation [J] . Monticelli Laurel A., Buck Michael D., Flamar Anne-Laure, Nature immunology . 2016,第6期

机译：精氨酸酶1是控制2型炎症的先天淋巴样细胞固有代谢检查点
2. INNATE LYMPHOID CELL FUNCTION IN ALLERGIC INFLAMMATION: ARGINASE 1 IS A CRITICAL METABOLIC CHECKPOINT CONTROLLING TYPE 2 INFLAMMATION [J] . Monticelli L. A., Buck M. D., Flamar A. -L., Cytokine . 2016,第Null期

机译：过敏性炎症中的固有淋巴细胞功能：精氨酸酶1是控制2型炎症的关键代谢检查点
3. INNATE LYMPHOID CELL FUNCTION IN ALLERGIC INFLAMMATION: ARGINASE 1 IS A CRITICAL METABOLIC CHECKPOINT CONTROLLING TYPE 2 INFLAMMATION [J] . Monticelli L. A., Buck M. D., Flamar A. -L., Cytokine . 2016,第Null期

机译：在过敏性炎症中的先天淋巴细胞功能：氨基酶1是一种临界代谢检查点控制2型炎症
4. Innate Immunity, Inflammation and Colorectal Cancer [C] . Kepeng Wang, Sergei Grivennikov, Michael Karin Else Kroener-Fresenius Symposium . 2013

机译：先天免疫，炎症和结直肠癌
5. Arginase-I expression by innate lymphoid cells during fetal development, adult homeostasis, and inflammation. [D] . Bando, Jennifer Kaoru. 2014

机译：在胎儿发育，成年体内稳态和炎症过程中，先天淋巴样细胞表达精氨酸酶-1。
6. Arginase 1 is an innate lymphoid cell-intrinsic metabolic checkpoint controlling type 2 inflammation [O] . Laurel A Monticelli, Michael D Buck, Anne-Laure Flamar, -1

机译：精氨酸酶1是控制2型炎症的先天性淋巴样细胞固有代谢检查点
7. Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation. [O] . Monticelli, Laurel A, Buck, Michael D, Flamar, Anne-Laure, 2016

机译：精氨酸酶1是控制2型炎症的先天淋巴细胞内在代谢检查点。

Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation

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