{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:58:14Z","timestamp":1792195094707,"version":"4.4.0"},"reference-count":89,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T00:00:00Z","timestamp":1572393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["677006"],"award-info":[{"award-number":["677006"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001822","name":"Austrian Academy of Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001822","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["PZ00P3_180011\/1"],"award-info":[{"award-number":["PZ00P3_180011\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Immunity"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1016\/j.immuni.2019.10.014","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T10:49:10Z","timestamp":1574765350000},"page":"1074-1087.e9","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":125,"title":["Type I Interferon Signaling Disrupts the Hepatic Urea Cycle and Alters Systemic Metabolism to Suppress T Cell Function"],"prefix":"10.1016","volume":"51","author":[{"given":"Alexander","family":"Lercher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anannya","family":"Bhattacharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra M.","family":"Popa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Caldera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz F.","family":"Schlapansky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatoon","family":"Baazim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Agerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"G\u00fcrtl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Kosack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"M\u00e1jek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia S.","family":"Brunner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dijana","family":"Vitko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Pinter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob-Wendelin","family":"Genger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Orlova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Pikor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Reil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ozsv\u00e1r-Kozma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Kalinke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Ludewig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Moriggl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiryn L.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Menche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul N.","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gernot","family":"Schabbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Trauner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristaps","family":"Klavins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0597-1976","authenticated-orcid":false,"given":"Andreas","family":"Bergthaler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.immuni.2019.10.014_bib1","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.2353\/ajpath.2006.051296","article-title":"Systemic viral infections and collateral damage in the liver","volume":"168","author":"Adams","year":"2006","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.immuni.2019.10.014_bib2","series-title":"GeneReviews","article-title":"Urea cycle disorders overview","author":"Mew","year":"2003"},{"key":"10.1016\/j.immuni.2019.10.014_bib3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41590-019-0397-y","article-title":"CD8+ T\u00a0cells induce cachexia during chronic viral infection","volume":"20","author":"Baazim","year":"2019","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2019.10.014_bib88","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jprot.2010.10.002","article-title":"Proteomic analysis of human cataract aqueous humour: Comparison of one-dimensional gel LCMS with two-dimensional LCMS of unlabelled and iTRAQ\u00ae-labelled specimens","volume":"74","author":"Bennett","year":"2011","journal-title":"J Proteomics"},{"key":"10.1016\/j.immuni.2019.10.014_bib4","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.immuni.2015.10.013","article-title":"Superoxide dismutase 1 protects hepatocytes from type I interferon-driven oxidative damage","volume":"43","author":"Bhattacharya","year":"2015","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2019.10.014_bib5","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"10.1016\/j.immuni.2019.10.014_bib85","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jprot.2013.02.022","article-title":"Isobar(PTM): a software tool for the quantitative analysis of post-translationally modified proteins","volume":"90","author":"Breitwieser","year":"2013","journal-title":"J Proteomics"},{"key":"10.1016\/j.immuni.2019.10.014_bib6","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1021\/pr1012784","article-title":"General statistical modeling of data from protein relative expression isobaric tags","volume":"10","author":"Breitwieser","year":"2011","journal-title":"J.\u00a0Proteome Res."},{"key":"10.1016\/j.immuni.2019.10.014_bib7","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.cell.2017.04.004","article-title":"Metabolic instruction of immunity","volume":"169","author":"Buck","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.immuni.2019.10.014_bib8","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41568-018-0050-3","article-title":"Polyamine metabolism and cancer: treatments, challenges and opportunities","volume":"18","author":"Casero","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.immuni.2019.10.014_bib9","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1182\/blood-2006-05-023770","article-title":"Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon","volume":"109","author":"Cervantes-Barragan","year":"2007","journal-title":"Blood"},{"key":"10.1016\/j.immuni.2019.10.014_bib10","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.cell.2015.08.016","article-title":"Metabolic competition in the tumor microenvironment is a driver of cancer progression","volume":"162","author":"Chang","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.immuni.2019.10.014_bib11","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1158\/0008-5472.CAN-06-1945","article-title":"Pegylated recombinant human arginase (rhArg-peg5,000mw) inhibits the in\u00a0vitro and in\u00a0vivo proliferation of human hepatocellular carcinoma through arginine depletion","volume":"67","author":"Cheng","year":"2007","journal-title":"Cancer Res."},{"key":"10.1016\/j.immuni.2019.10.014_bib12","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4049\/jimmunol.1501668","article-title":"Hepatocytes as immunological agents","volume":"196","author":"Crispe","year":"2016","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.immuni.2019.10.014_bib13","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nrn2297","article-title":"From inflammation to sickness and depression: when the immune system subjugates the brain","volume":"9","author":"Dantzer","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.immuni.2019.10.014_bib14","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13045-018-0612-6","article-title":"Metabolic therapy with PEG-arginase induces a sustained complete remission in immunotherapy-resistant melanoma","volume":"11","author":"De Santo","year":"2018","journal-title":"J.\u00a0Hematol. Oncol."},{"key":"10.1016\/j.immuni.2019.10.014_bib15","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1136\/jmedgenet-2016-103937","article-title":"Kinetic mutations in argininosuccinate synthetase deficiency: characterisation and in\u00a0vitro correction by substrate supplementation","volume":"53","author":"Diez-Fernandez","year":"2016","journal-title":"J.\u00a0Med. Genet."},{"key":"10.1016\/j.immuni.2019.10.014_bib16","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1053\/j.gastro.2013.11.001","article-title":"Metabolic phenotyping and systems biology approaches to understanding metabolic syndrome and fatty liver disease","volume":"146","author":"Dumas","year":"2014","journal-title":"Gastroenterology"},{"key":"10.1016\/j.immuni.2019.10.014_bib17","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1038\/bjc.2012.106","article-title":"Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase","volume":"106","author":"Feun","year":"2012","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.immuni.2019.10.014_bib18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1158\/2326-6066.CIR-16-0297","article-title":"Myeloid-derived suppressor cells","volume":"5","author":"Gabrilovich","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"10.1016\/j.immuni.2019.10.014_bib19","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.cell.2016.09.031","article-title":"L-arginine modulates T\u00a0cell metabolism and enhances survival and anti-tumor activity","volume":"167","author":"Geiger","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.immuni.2019.10.014_bib20","doi-asserted-by":"crossref","first-page":"20022","DOI":"10.1074\/jbc.M109.021089","article-title":"Argininosuccinate synthetase is a functional target for a snake venom anti-hypertensive peptide: role in arginine and nitric oxide production","volume":"284","author":"Guerreiro","year":"2009","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.immuni.2019.10.014_bib21","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1084\/jem.189.10.1555","article-title":"Noncytopathic clearance of lymphocytic choriomeningitis virus from the hepatocyte","volume":"189","author":"Guidotti","year":"1999","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2019.10.014_bib22","article-title":"Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression","author":"Hafemeister","year":"2019","journal-title":"bioRxiv"},{"key":"10.1016\/j.immuni.2019.10.014_bib23","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nature21065","article-title":"Single-cell spatial reconstruction reveals global division of labour in the mammalian liver","volume":"542","author":"Halpern","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2019.10.014_bib24","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nature21363","article-title":"Inflammation, metaflammation and immunometabolic disorders","volume":"542","author":"Hotamisligil","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2019.10.014_bib25","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/ni.2691","article-title":"Immune surveillance by the liver","volume":"14","author":"Jenne","year":"2013","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2019.10.014_bib26","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.immuni.2015.02.005","article-title":"Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization","volume":"42","author":"Jha","year":"2015","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2019.10.014_bib27","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1016\/j.cell.2018.10.001","article-title":"Distinct regulation of Th17 and Th1 cell differentiation by glutaminase-dependent metabolism","volume":"175","author":"Johnson","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.immuni.2019.10.014_bib84","doi-asserted-by":"crossref","first-page":"3253","DOI":"10.1182\/blood-2006-06-027599","article-title":"Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia","volume":"108","author":"Kamphuis","year":"2006","journal-title":"Blood"},{"key":"10.1016\/j.immuni.2019.10.014_bib28","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.immuni.2019.10.014_bib29","doi-asserted-by":"crossref","first-page":"11289","DOI":"10.1038\/s41598-017-10637-y","article-title":"The lipid-sensor TREM2 aggravates disease in a model of LCMV-induced hepatitis","volume":"7","author":"Kosack","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.immuni.2019.10.014_bib30","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.cell.2015.02.010","article-title":"Homeostasis, inflammation, and disease susceptibility","volume":"160","author":"Kotas","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.immuni.2019.10.014_bib31","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1101\/gr.092759.109","article-title":"Circos: an information aesthetic for comparative genomics","volume":"19","author":"Krzywinski","year":"2009","journal-title":"Genome Res."},{"key":"10.1016\/j.immuni.2019.10.014_bib32","series-title":"Liver Immunology","first-page":"159","article-title":"Viral diseases of the liver","author":"Lalazar","year":"2014"},{"key":"10.1016\/j.immuni.2019.10.014_bib33","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/j.1755-148X.2010.00798.x","article-title":"Recombinant human arginase inhibits the in\u00a0vitro and in\u00a0vivo proliferation of human melanoma by inducing cell cycle arrest and apoptosis","volume":"24","author":"Lam","year":"2011","journal-title":"Pigment Cell Melanoma Res."},{"key":"10.1016\/j.immuni.2019.10.014_bib34","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1186\/gb-2014-15-2-r29","article-title":"voom: precision weights unlock linear model analysis tools for RNA-seq read counts","volume":"15","author":"Law","year":"2014","journal-title":"Genome Biol."},{"key":"10.1016\/j.immuni.2019.10.014_bib35","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1016\/j.cell.2018.07.019","article-title":"Urea cycle dysregulation generates clinically relevant genomic and biochemical signatures","volume":"174","author":"Lee","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.immuni.2019.10.014_bib36","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1021\/pr200047c","article-title":"A proton nuclear magnetic resonance metabonomics approach for biomarker discovery in nonalcoholic fatty liver disease","volume":"10","author":"Li","year":"2011","journal-title":"J.\u00a0Proteome Res."},{"key":"10.1016\/j.immuni.2019.10.014_bib37","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/s41586-019-0996-7","article-title":"p53 regulation of ammonia metabolism through urea cycle controls polyamine biosynthesis","volume":"567","author":"Li","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2019.10.014_bib38","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"10.1016\/j.immuni.2019.10.014_bib39","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.cmet.2016.12.011","article-title":"Serine is an essential metabolite for effector T\u00a0cell expansion","volume":"25","author":"Ma","year":"2017","journal-title":"Cell Metab."},{"key":"10.1016\/j.immuni.2019.10.014_bib86","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1002\/pmic.200401063","article-title":"Sample preparation and digestion for proteomic analyses using spin filters","volume":"5","author":"Manza","year":"2005","journal-title":"Proteomics"},{"key":"10.1016\/j.immuni.2019.10.014_bib40","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nri3787","article-title":"Type I interferons in infectious disease","volume":"15","author":"McNab","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.immuni.2019.10.014_bib41","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2019.10.014_bib42","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1152\/physrev.1990.70.3.701","article-title":"Nitrogen metabolism and ornithine cycle function","volume":"70","author":"Meijer","year":"1990","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.immuni.2019.10.014_bib43","first-page":"329","article-title":"Targeted somatic mutagenesis in the mouse epidermis","volume":"289","author":"Metzger","year":"2005","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.immuni.2019.10.014_bib44","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1038\/ni.3867","article-title":"Metabolic shift induced by systemic activation of T\u00a0cells in PD-1-deficient mice perturbs brain monoamines and emotional behavior","volume":"18","author":"Miyajima","year":"2017","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2019.10.014_bib45","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.cell.2015.12.032","article-title":"Parsing the interferon transcriptional network and its disease associations","volume":"164","author":"Mostafavi","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.immuni.2019.10.014_bib46","doi-asserted-by":"crossref","first-page":"9683","DOI":"10.1128\/JVI.01347-16","article-title":"Inhibition of polyamine biosynthesis is a broad-spectrum strategy against RNA viruses","volume":"90","author":"Mounce","year":"2016","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.immuni.2019.10.014_bib83","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1126\/science.8009221","article-title":"Functional role of type I and type II interferons in antiviral defense","volume":"264","author":"Muller","year":"1994","journal-title":"Science"},{"key":"10.1016\/j.immuni.2019.10.014_bib47","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ni.3323","article-title":"Amino acid auxotrophy as a system of immunological control nodes","volume":"17","author":"Murray","year":"2016","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2019.10.014_bib48","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.immuni.2015.08.023","article-title":"The cellular and molecular basis of translational immunometabolism","volume":"43","author":"Norata","year":"2015","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2019.10.014_bib89","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1074\/mcp.T500030-MCP200","article-title":"Parts per million mass accuracy on an Orbitrap mass spectrometer via lock mass injection into a C-trap","volume":"4","author":"Olsen","year":"2005","journal-title":"Mol Cell Proteomics"},{"key":"10.1016\/j.immuni.2019.10.014_bib49","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1084\/jem.20151570","article-title":"Immunometabolism governs dendritic cell and macrophage function","volume":"213","author":"O\u2019Neill","year":"2016","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2019.10.014_bib50","doi-asserted-by":"crossref","first-page":"R733","DOI":"10.1016\/j.cub.2012.07.029","article-title":"Evolution of inflammatory diseases","volume":"22","author":"Okin","year":"2012","journal-title":"Curr. Biol."},{"key":"10.1016\/j.immuni.2019.10.014_bib51","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/nm.3856","article-title":"Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells","volume":"21","author":"Pallett","year":"2015","journal-title":"Nat. Med."},{"key":"10.1016\/j.immuni.2019.10.014_bib52","doi-asserted-by":"crossref","first-page":"e1001759","DOI":"10.1371\/journal.pbio.1001759","article-title":"Direct type I IFN but not MDA5\/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation","volume":"12","author":"Pantel","year":"2014","journal-title":"PLoS Biol."},{"key":"10.1016\/j.immuni.2019.10.014_bib53","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.immuni.2013.04.005","article-title":"Metabolic pathways in immune cell activation and quiescence","volume":"38","author":"Pearce","year":"2013","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2019.10.014_bib54","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/nature08097","article-title":"Enhancing CD8 T-cell memory by modulating fatty acid metabolism","volume":"460","author":"Pearce","year":"2009","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2019.10.014_bib55","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/s41586-018-0697-7","article-title":"Autophagy maintains tumour growth through circulating arginine","volume":"563","author":"Poillet-Perez","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2019.10.014_bib56","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nri3169","article-title":"Living in the liver: hepatic infections","volume":"12","author":"Protzer","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.immuni.2019.10.014_bib57","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nature15529","article-title":"Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis","volume":"527","author":"Rabinovich","year":"2015","journal-title":"Nature"},{"issue":"2, Suppl 1","key":"10.1016\/j.immuni.2019.10.014_bib58","doi-asserted-by":"crossref","first-page":"S54","DOI":"10.1002\/hep.21060","article-title":"The liver as an immunological organ","volume":"43","author":"Racanelli","year":"2006","journal-title":"Hepatology"},{"key":"10.1016\/j.immuni.2019.10.014_bib59","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nri1573","article-title":"Immunology of hepatitis B virus and hepatitis C virus infection","volume":"5","author":"Rehermann","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.immuni.2019.10.014_bib60","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.cell.2018.07.016","article-title":"Cooperative metabolic adaptations in the host can favor asymptomatic infection and select for attenuated virulence in an enteric pathogen","volume":"175","author":"Sanchez","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.immuni.2019.10.014_bib61","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature09907","article-title":"A diverse range of gene products are effectors of the type I interferon antiviral response","volume":"472","author":"Schoggins","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2019.10.014_bib82","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/gene.20039","article-title":"Efficient temporally controlled targeted somatic mutagenesis in hepatocytes of the mouse","volume":"39","author":"Schuler","year":"2004","journal-title":"Genesis"},{"key":"10.1016\/j.immuni.2019.10.014_bib62","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/ni.2556","article-title":"Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T\u00a0cell differentiation","volume":"14","author":"Sinclair","year":"2013","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2019.10.014_bib63","doi-asserted-by":"crossref","DOI":"10.2202\/1544-6115.1027","article-title":"Linear models and empirical bayes methods for assessing differential expression in microarray experiments","volume":"3","author":"Smyth","year":"2004","journal-title":"Stat. Appl. Genet. Mol. Biol."},{"key":"10.1016\/j.immuni.2019.10.014_bib64","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.jhep.2011.01.031","article-title":"Serum metabolomics reveals \u03b3-glutamyl dipeptides as biomarkers for discrimination among different forms of liver disease","volume":"55","author":"Soga","year":"2011","journal-title":"J.\u00a0Hepatol."},{"key":"10.1016\/j.immuni.2019.10.014_bib65","doi-asserted-by":"crossref","first-page":"170140","DOI":"10.1038\/sdata.2017.140","article-title":"Targeted metabolomics and medication classification data from participants in the ADNI1 cohort","volume":"4","author":"St John-Williams","year":"2017","journal-title":"Sci. Data"},{"key":"10.1016\/j.immuni.2019.10.014_bib66","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.immuni.2019.10.014_bib67","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1128\/iai.6.4.501-507.1972","article-title":"Enhanced growth of a murine coronavirus in transformed mouse cells","volume":"6","author":"Sturman","year":"1972","journal-title":"Infect. Immun."},{"key":"10.1016\/j.immuni.2019.10.014_bib68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11011-012-9370-2","article-title":"Systemic inflammation and ammonia in hepatic encephalopathy","volume":"28","author":"Tranah","year":"2013","journal-title":"Metab. Brain Dis."},{"key":"10.1016\/j.immuni.2019.10.014_bib69","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Tissue-based map of the human proteome","volume":"347","author":"Uhl\u00e9n","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.immuni.2019.10.014_bib70","doi-asserted-by":"crossref","first-page":"25815","DOI":"10.1074\/jbc.C116.763623","article-title":"Proliferating helper T\u00a0cells require rictor\/mTORC2 complex to integrate signals from limiting environmental amino acids","volume":"291","author":"Van de Velde","year":"2016","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.immuni.2019.10.014_bib71","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/BF01797914","article-title":"The role of the liver in metabolic homeostasis: implications for inborn errors of metabolism","volume":"14","author":"van den Berghe","year":"1991","journal-title":"J.\u00a0Inherit. Metab. Dis."},{"key":"10.1016\/j.immuni.2019.10.014_bib72","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.cell.2009.06.036","article-title":"Redefining chronic viral infection","volume":"138","author":"Virgin","year":"2009","journal-title":"Cell"},{"key":"10.1016\/j.immuni.2019.10.014_bib73","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1126\/science.aar3932","article-title":"An evolutionary perspective on immunometabolism","volume":"363","author":"Wang","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.immuni.2019.10.014_bib74","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/bmb.2003.494031050249","article-title":"The urea cycle: teaching intermediary metabolism in a physiological setting","volume":"31","author":"Watford","year":"2003","journal-title":"Biochem. Mol. Biol. Educ."},{"key":"10.1016\/j.immuni.2019.10.014_bib75","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T\u00a0cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.immuni.2019.10.014_bib87","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Wisniewski","year":"2009","journal-title":"Nat Methods"},{"key":"10.1016\/j.immuni.2019.10.014_bib76","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00726-008-0210-y","article-title":"Arginine metabolism and nutrition in growth, health and disease","volume":"37","author":"Wu","year":"2009","journal-title":"Amino Acids"},{"key":"10.1016\/j.immuni.2019.10.014_bib77","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/j.immuni.2016.06.006","article-title":"Type 1 interferons induce changes in core metabolism that are critical for immune function","volume":"44","author":"Wu","year":"2016","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2019.10.014_bib78","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1016\/j.cell.2015.11.045","article-title":"Limiting cholesterol biosynthetic flux spontaneously engages type I IFN signaling","volume":"163","author":"York","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.immuni.2019.10.014_bib79","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/978-3-319-15774-0_10","article-title":"Immune memory and exhaustion: clinically relevant lessons from the LCMV model","volume":"850","author":"Zehn","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.immuni.2019.10.014_bib80","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/cmi.2015.97","article-title":"Hepatocytes: a key cell type for innate immunity","volume":"13","author":"Zhou","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"10.1016\/j.immuni.2019.10.014_bib81","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1084\/jem.164.4.1075","article-title":"T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I-restricted virus-specific cytotoxic T\u00a0cells as a physiological correlate of the 51Cr-release assay?","volume":"164","author":"Zinkernagel","year":"1986","journal-title":"J.\u00a0Exp. Med."}],"container-title":["Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1074761319304583?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1074761319304583?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T08:06:31Z","timestamp":1761033991000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1074761319304583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":89,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["S1074761319304583"],"URL":"https:\/\/doi.org\/10.1016\/j.immuni.2019.10.014","relation":{},"ISSN":["1074-7613"],"issn-type":[{"value":"1074-7613","type":"print"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Type I Interferon Signaling Disrupts the Hepatic Urea Cycle and Alters Systemic Metabolism to Suppress T Cell Function","name":"articletitle","label":"Article Title"},{"value":"Immunity","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.immuni.2019.10.014","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Author(s). Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}