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.
authors.affiliation: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, New York, USA.
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Monticelli
authors.affiliation: Department of Immunometabolism, Max Plank Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Buck
authors.affiliation: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, New York, USA.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Flamar
authors.affiliation: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, New York, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Saenz
authors.affiliation: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, New York, USA.
authors.forename: Elia D
authors.initials: ED
authors.lastname: Tait Wojno
authors.affiliation: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, New York, USA.
authors.forename: Naomi A
authors.initials: NA
authors.lastname: Yudanin
authors.affiliation: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, New York, USA.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Osborne
authors.affiliation: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, New York, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hepworth
authors.affiliation: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, New York, USA.
authors.forename: Sara V
authors.initials: SV
authors.lastname: Tran
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hans-Reimer
authors.initials: HR
authors.lastname: Rodewald
authors.affiliation: Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Hardik
authors.identifier: 0000-0001-8408-5686
authors.initials: H
authors.lastname: Shah
authors.affiliation: Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Cross
authors.affiliation: Division of Cardiovascular Surgery, Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Diamond
authors.affiliation: Division of Cardiovascular Surgery, Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Cantu
authors.affiliation: Division of Cardiovascular Surgery, Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Christie
authors.affiliation: Department of Immunometabolism, Max Plank Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Erika L
authors.initials: EL
authors.lastname: Pearce
authors.affiliation: Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, New York, USA.
authors.forename: David
authors.initials: D
authors.lastname: Artis
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate; D008213:Lymphocyte Activation / Q000235:genetics; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011014:Pneumonia / Q000276:immunology*; D011073:Polyamines / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D011073:Polyamines; C544448:Arg1 protein, mouse; D001119:Arginase