{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:17:39Z","timestamp":1793038659419,"version":"4.5.0"},"reference-count":58,"publisher":"National Academy of Sciences","issue":"45","license":[{"start":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI159210"],"award-info":[{"award-number":["AI159210"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["DK077653"],"award-info":[{"award-number":["DK077653"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["DK127540"],"award-info":[{"award-number":["DK127540"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,11,8]]},"abstract":"<jats:p>\n                    Group 3 innate lymphoid cells (ILC3s) are ROR\u03b3T\n                    <jats:sup>+<\/jats:sup>\n                    lymphocytes that are predominately enriched in mucosal tissues and produce IL-22 and IL-17A. They are the innate counterparts of Th17 cells. While Th17 lymphocytes utilize unique metabolic pathways in their differentiation program, it is unknown whether ILC3s make similar metabolic adaptations. We employed single-cell RNA sequencing and metabolomic profiling of intestinal ILC subsets to identify an enrichment of polyamine biosynthesis in ILC3s, converging on the rate-limiting enzyme ornithine decarboxylase (ODC1). In vitro and in\u00a0vivo studies demonstrated that exogenous supplementation with the polyamine putrescine or its biosynthetic substrate, ornithine, enhanced ILC3 production of IL-22. Conditional deletion of ODC1 in ILC3s impaired mouse antibacterial defense against\n                    <jats:italic>Citrobacter rodentium<\/jats:italic>\n                    infection, which was associated with a decrease in anti-microbial peptide production by the intestinal epithelium. Furthermore, in a model of anti-CD40 colitis, deficiency of ODC1 in ILC3s markedly reduced the production of IL-22 and severity of inflammatory colitis. We conclude that ILC3-intrinsic polyamine biosynthesis facilitates efficient defense against enteric pathogens as well as exacerbates autoimmune colitis, thus representing an attractive target to modulate ILC3 function in intestinal disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2214900119","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T15:13:49Z","timestamp":1666624429000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":41,"title":["Ornithine decarboxylase supports ILC3 responses in infectious and autoimmune colitis through positive regulation of IL-22 transcription"],"prefix":"10.1073","volume":"119","author":[{"given":"Vincent","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-2164","authenticated-orcid":false,"given":"Siyan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110"},{"name":"Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tihana","family":"Trsan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1331-7424","authenticated-orcid":false,"given":"Jennifer K.","family":"Bando","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Avila-Pacheco","sequence":"additional","affiliation":[{"name":"Broad Institute, Cambridge, MA 02412"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Cleveland","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, H. Lee Moffitt Cancer Center &amp; Research Institute, Tampa, FL 33612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clary","family":"Clish","sequence":"additional","affiliation":[{"name":"Broad Institute, Cambridge, MA 02412"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramnik J.","family":"Xavier","sequence":"additional","affiliation":[{"name":"Broad Institute, Cambridge, MA 02412"},{"name":"Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Cambridge Street, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5222-4987","authenticated-orcid":false,"given":"Marco","family":"Colonna","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,10,24]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.017"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3484"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3489"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3057"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13047"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.030"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01298"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02010"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700155"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.10.017"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.06.019"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0425-y"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11813"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1214914"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096472"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.4.1449"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.11"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180549"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.07.043"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R116.731661"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0050-3"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2007.tb03887.x"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-011-0987-y"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.04.021"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-013-1550-9"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(87)90184-5"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(73)80044-4"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.16.7804"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.09.021"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(87)90060-8"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0162-3109(91)90016-R"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2001.5177"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.06.007"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc4275"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1614958114"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.05.045"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.03.003"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3421"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.036"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.09.004"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.06.009"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.71"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.11.001"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1720"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254009"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151403"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08949"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00680-1"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2019.00016"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1097\/00054725-200409000-00006"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21224"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22212-1"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.11.005"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.04.037"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01024-x"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-019-02719-0"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.315622"},{"key":"e_1_3_4_58_2","doi-asserted-by":"crossref","unstructured":"V. Peng M. Colonna Ornithine decarboxylase supports ILC3 responses in infectious and autoimmune colitis through positive regulation of IL-22 transcription. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE214152. Deposited 25 September 2022.","DOI":"10.1073\/pnas.2214900119"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2214900119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T08:34:01Z","timestamp":1695285241000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2214900119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,24]]},"references-count":58,"journal-issue":{"issue":"45","published-print":{"date-parts":[[2022,11,8]]}},"alternative-id":["10.1073\/pnas.2214900119"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2214900119","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,24]]},"assertion":[{"value":"2022-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2214900119"}}