{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:47:06Z","timestamp":1788580026678,"version":"build-2803163510"},"reference-count":73,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"107","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2025,5,30]]},"abstract":"<jats:p>\n            Interferonopathies drive autoimmunity but can also impair host responses to pathogens, including viral infections. To better understand viral susceptibility of patients with\n            <jats:italic toggle=\"yes\">STAT1<\/jats:italic>\n            gain-of-function (GOF) mutations, we generated conditional knockin mouse models to elucidate disease mechanisms and relevance of different immune subsets. Virally infected\n            <jats:italic toggle=\"yes\">Stat1<\/jats:italic>\n            GOF mice exhibited impaired early IFN-\u03b3 production from innate lymphocytes and lethality because of excess prolonged multicytokine production. The presence of the\n            <jats:italic toggle=\"yes\">Stat1<\/jats:italic>\n            GOF allele resulted in premature usage of interferon-stimulated gene factor 3 (ISGF3) over the normal STAT4\u2013AP-1\u2013dependent transcriptomic program in activated innate lymphocytes. Administration of anti\u2013IFN-\u03b3 antibodies in wild-type (WT) mice after infection phenocopied\n            <jats:italic toggle=\"yes\">Stat1<\/jats:italic>\n            GOF mice presenting exaggerated inflammation despite viral control. Conversely, early administration of exogenous IFN-\u03b3 to infected\n            <jats:italic toggle=\"yes\">Stat1<\/jats:italic>\n            GOF mice prevented lethality and exaggerated cytokine response. Although\n            <jats:italic toggle=\"yes\">Stat1<\/jats:italic>\n            GOF mutations facilitate IFN-\u03b3\u2013mediated autoimmunity, early IFN-\u03b3 responses to viral infection via a normal STAT4 program were impaired, leading to overcompensated inflammatory responses in\n            <jats:italic toggle=\"yes\">Stat1<\/jats:italic>\n            GOF mice.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.ado5986","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T17:59:00Z","timestamp":1748627940000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["An activating\n            <i>Stat1<\/i>\n            mutant disrupts normal STAT4 innate lymphocyte programs during viral infection"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5440-4594","authenticated-orcid":true,"given":"Rachael L.","family":"Philips","sequence":"first","affiliation":[{"name":"Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch (MIIB), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), Bethesda, MD 20892, USA."},{"name":"National Institutes of General Medical Sciences, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9458-1445","authenticated-orcid":true,"given":"Yi-Chu","family":"Liao","sequence":"additional","affiliation":[{"name":"Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch (MIIB), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7538-094X","authenticated-orcid":true,"given":"Colleen M.","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6403-9364","authenticated-orcid":true,"given":"Tasha A.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Lymphocyte Signaling Unit, MIIB, NIAMS, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9065-4574","authenticated-orcid":true,"given":"Kan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Biodata Mining and Discovery Section, NIAMS, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch (MIIB), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5617-6494","authenticated-orcid":true,"given":"Justin","family":"Shayne","sequence":"additional","affiliation":[{"name":"Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch (MIIB), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6852-5661","authenticated-orcid":true,"given":"Chen","family":"Yao","sequence":"additional","affiliation":[{"name":"Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch (MIIB), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8062-9033","authenticated-orcid":true,"given":"Joseph C.","family":"Sun","sequence":"additional","affiliation":[{"name":"Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA."},{"name":"Immunology and Microbial Pathogenesis Program, Graduate School of Medical Sciences, Weill Cornell Medical College, New York, NY 10065, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4168-4894","authenticated-orcid":true,"given":"Heather D.","family":"Hickman","sequence":"additional","affiliation":[{"name":"Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology (LCIM), NIAID, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Milner","sequence":"additional","affiliation":[{"name":"Division of Pediatric Allergy Immunology and Rheumatology, Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3207-5464","authenticated-orcid":true,"given":"Steve","family":"Holland","sequence":"additional","affiliation":[{"name":"Immunopathogenesis Section, LCIM, NIAID, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5668-9319","authenticated-orcid":true,"given":"Yuka","family":"Kanno","sequence":"additional","affiliation":[{"name":"Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch (MIIB), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4994-9500","authenticated-orcid":true,"given":"Michail S.","family":"Lionakis","sequence":"additional","affiliation":[{"name":"Fungal Pathogenesis Section, LCIM, NIAID, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6456-9752","authenticated-orcid":true,"given":"John J.","family":"O\u2019Shea","sequence":"additional","affiliation":[{"name":"Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch (MIIB), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00633-9"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.633821"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.09.023"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.03.016"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110958"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.01.052"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1100102"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-679902"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.11.054"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2018.31"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.ade7028"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.654406"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2020.01.004"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2012.04.011"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01433"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxz079"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1183273"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0501-42"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-015-0412-3"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048793"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd4570"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd4585"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abl4340"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.052"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300837"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(97)00091-6"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.4.1665"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.12.6803"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.3.1146"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.7.2818-2824.1994"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.10.4038-4044.1993"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/382171a0"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/382174a0"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.4.1045"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074900"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070401"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09982-5"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0373-x"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0176-1"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00836-7"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20182009"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-020-1929-3"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00790-6"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00909-1"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/76940"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.07.060"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.04.029"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.09.002"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13300"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00307-19"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235214"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235208"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1237568"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090331"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)45453-6"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.03.031"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2901"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00300-5"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02336-06"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-023-01634-0"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.07.020"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210554"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199142050-00003"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00429-3"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1112064108"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2008.06.001"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.03.005"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13072-019-0287-4"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq033"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku365"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2014.03.029"}],"container-title":["Science Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciimmunol.ado5986","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T17:59:08Z","timestamp":1748627948000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.ado5986"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,30]]},"references-count":73,"journal-issue":{"issue":"107","published-print":{"date-parts":[[2025,5,30]]}},"alternative-id":["10.1126\/sciimmunol.ado5986"],"URL":"https:\/\/doi.org\/10.1126\/sciimmunol.ado5986","relation":{},"ISSN":["2470-9468"],"issn-type":[{"value":"2470-9468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,30]]},"assertion":[{"value":"2024-02-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eado5986"}}