ArticleNature immunology2016
Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation.
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Article in Nature immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers.
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183citing papers in PubMed
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183 citing papers in PubMed.
- Innate immunity: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Monocyte infiltration induces CNS arginine catabolism to fuel neuroinflammation.Nature immunology · 2026Article
- Review
- IL-33 promotes transcriptional and metabolic adaptations of tissue-resident Th2 cells.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- RIPK3 Orchestrates Scar-Associated Macrophage Dysfunction to Drive Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-cell analysis of recruited ILC2 cell fate during transition from circulation to establishment of tissue residency.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Involvement of increased arginase-1The Journal of international medical research · 2026Article
- SLC7A8 is essential for metabolic fitness and function of Th2 cells.The Journal of experimental medicine · 2026Article
- The IL-33-ILC2 axis: a key regulator of type 2 immunity in respiratory disease.Frontiers in immunology · 2026Review
- The metabolic environment within solid tumors drives a complex crosstalk between macrophages and NK cells.Frontiers in immunology · 2026Review
- Construction of a Bioactive ECM Interface Enables Concurrent Suppression of Foreign Body Reaction, Inflammation, and Promotion of Urethral Regeneration.Biomaterials research · 2026Article
- Large neutral amino acid uptake and mTOR activation within CD4 T cells coordinate type 2 immunity and host resistance toDiscovery immunology · 2026Article
- ASNS-dependent asparagine availability supports intestinal ILC2 responses and type 2 immunity under nutrient-limited conditions.Frontiers in immunology · 2026Article
- Stem cell factor 248 shapes ILC2 transcriptional programs and promotes mucosal inflammation in allergic asthma.Frontiers in immunology · 2026Article
- Glycolytic reprogramming in cancer: immune crosstalk, nutrient competition, and supportive care perspectives.Frontiers in immunology · 2026Review
- Mechanisms of action of retinal microglia in diabetic retinopathy (Review).International journal of molecular medicine · 2025Review
- Arginine Metabolism in Decidual Macrophages During Pregnancy.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Review
- The immunoproteasome regulates ILC2 responses by modulating mitochondrial capacity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Multifaceted Role of ILCs in Metabolic Adaptations: From Adult to Neonate.European journal of immunology · 2025Review
- Global proteomic analysis ofmSystems · 2025Article
123 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors.
Laurel A MonticelliJill 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.
Michael D BuckDepartment of Immunometabolism, Max Plank Institute of Immunobiology and Epigenetics, Freiburg, Germany.
Anne-Laure FlamarJill 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.
Steven A SaenzJill 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.
Elia D Tait WojnoJill 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.
Naomi A YudaninJill 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.
Lisa C OsborneJill 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.
Matthew R HepworthJill 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.
Sara V TranJill 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.
Hans-Reimer RodewaldDivision of Cellular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Hardik ShahDonald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, New York, USA.ORCID 0000-0001-8408-5686
Justin R CrossDonald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Joshua M DiamondDivision of Cardiovascular Surgery, Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Edward CantuDivision of Cardiovascular Surgery, Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jason D ChristieDivision of Cardiovascular Surgery, Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Erika L PearceDepartment of Immunometabolism, Max Plank Institute of Immunobiology and Epigenetics, Freiburg, Germany.
David ArtisJill 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.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MTranscriptomics and Repertoire ProfilingP01AI106697 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Donna L. Farber · 2013 to 2026
$31.3MRegulation of protective immunity following enteric viral infectionU01AI095608 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI ARTIS, DAVID, SONNENBERG, GREGORY F · 2011 to 2025
$11.0MClinical Risk Factors for Primary Graft DysfunctionR01HL087115 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI CHRISTIE, JASON D · 2007 to 2017
$7.1MPARASITOLOGY: MODERN APPROACHEST32AI007532 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HERBERT, DE'BROSKI R · 1998 to 2022
$5.0MInnate immunity and inflammation following helminth infectionR01AI074878 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI ARTIS, DAVID · 2008 to 2019
$4.2MImmuno-regulation of GI nematode infectionR01AI061570 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI ARTIS, DAVID · 2004 to 2013
$4.1MGenetics of primary graft dysfunctionR01HL081619 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI CHRISTIE, JASON D · 2007 to 2011
$3.9MRegulation and function of innate lymphoid cells in the gutR01AI095466 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI ARTIS, DAVID · 2011 to 2022
$3.7MObesity, Inflammation, and Lung Injury After Lung TransplantationR01HL114626 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CHRISTIE, JASON D, LEDERER, DAVID J. · 2013 to 2016
$3.1MRole of anti-Col (V) immunity in primary graft dysfunctionR01HL096845 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI CHRISTIE, JASON D, WILKES, DAVID S · 2010 to 2013
$2.2MRegulation and function of innate lymphoid cells during influenza virus infectionR01AI102942 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI ARTIS, DAVID · 2013 to 2017
$2.1MNCI NIH HHS P30 CA008748NCI NIH HHS R01 CA181125NHLBI NIH HHS K12 HL090021NHLBI NIH HHS K23 HL116656NHLBI NIH HHS K23 HL121406NHLBI NIH HHS K24 HL115354NHLBI NIH HHS R01 HL081619NHLBI NIH HHS R01 HL087115NHLBI NIH HHS R01 HL096845NHLBI NIH HHS R01 HL114626NHLBI NIH HHS R03 HL135227NIAID NIH HHS P01 AI106697NIAID NIH HHS R01 AI061570NIAID NIH HHS R01 AI074878NIAID NIH HHS R01 AI091965NIAID NIH HHS R01 AI095466NIAID NIH HHS R01 AI097333NIAID NIH HHS R01 AI102942NIAID NIH HHS R21 AI083480NIAID NIH HHS R21 AI087990NIAID NIH HHS T32 AI007532NIAID NIH HHS U01 AI095608NIDDK NIH HHS F32 DK109630Wellcome Trust 105644
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.
Indexed as
AnimalsArginaseCell ProliferationCells, CulturedCytokinesGlycolysisHumansImmunity, InnateLymphocyte ActivationLymphocytesMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPneumoniaPolyaminesArg1 protein, mouseArginaseCytokinesPolyamines
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