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

   

Authors:	Monticelli, L. A.; Buck, M. D.; Flamar, A. L.; Saenz, S. A.; Wojno, E. D. T.; Yudanin, N. A.; Osborne, L. C.; Hepworth, M. R.; Tran, S. V.; Rodewald, H. R.; Shah, H.; Cross, J. R.; Diamond, J. M.; Cantu, E.; Christie, J. D.; Pearce, E. L.; Artis, D.
Article Title:	Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation
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.
Keywords:	infection; fibrosis; asthma; immunity; obstructive pulmonary-disease; l-arginine; alternatively activated macrophages; allergic lung inflammation; inflamed lung; airways
Journal Title:	Nature Immunology
Volume:	17
Issue:	6
ISSN:	1529-2908
Publisher:	Nature Publishing Group
Date Published:	2016-06-01
Start Page:	656
End Page:	665
Language:	English
ACCESSION:	WOS:000376162200010
DOI:	10.1038/ni.3421
PROVIDER:	wos
PMCID:	PMC4873382
PUBMED:	27043409
Notes:	Article -- Source: Wos

https://synapse.mskcc.org/synapse/works/has_related_data_chk/94947