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

TitleArginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation.
Publication TypeJournal Article
Year of Publication2016
AuthorsMonticelli, LA, Buck, MD, Flamar, A-L, Saenz, SA, Wojno, EDTait, Yudanin, NA, Osborne, LC, Hepworth, MR, Tran, SV, Rodewald, H-R, Shah, H, Cross, JR, Diamond, JM, Cantu, E, Christie, JD, Pearce, EL, Artis, D
JournalNat Immunol
Volume17
Issue6
Pagination656-65
Date Published2016 Apr 4
ISSN1529-2916
Abstract

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.

DOI10.1038/ni.3421
Alternate JournalNat. Immunol.
PubMed ID27043409
Grant ListP01 AI106697 / AI / NIAID NIH HHS / United States
R01 AI061570 / AI / NIAID NIH HHS / United States
R01 AI074878 / AI / NIAID NIH HHS / United States
R01 AI095466 / AI / NIAID NIH HHS / United States
R01 AI097333 / AI / NIAID NIH HHS / United States
R01 AI102942 / AI / NIAID NIH HHS / United States
U01 AI095608 / AI / NIAID NIH HHS / United States