{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:13:34Z","timestamp":1780524814226,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Type I interferons (IFN1s) mediate innate responses to microbial stimuli and regulate interleukin (IL)\u20101 and IL\u20101 receptor antagonist (Ra) production in human cells. This study explores interferon\u2010stimulated gene (ISG) alterations in the transcriptome of patients with gout and stimulated human primary cells in vitro in relation to serum urate concentrations. Peripheral blood mononuclear cells (PBMCs) and monocytes of patients with gout were primed in vitro with soluble urate, followed by lipopolysaccharide (LPS) stimulation. Separately, PBMCs were stimulated with various toll\u2010like receptor (TLR) ligands. RNA sequencing and IL\u20101Ra cytokine measurement were performed. STAT1 phosphorylation was assessed in urate\u2010treated monocytes. Cytokine responses to IFN\u2010\u03b2 were evaluated in PBMCs cultured with or without urate and restimulated with LPS and monosodium urate (MSU) crystals. Transcriptomics revealed suppressed IFN\u2010related signalling pathways in urate\u2010exposed PBMCs or monocytes which was supported by diminishment of phosphorylated STAT1. The stimulation of PBMCs with IFN\u2010\u03b2 did not modify the urate\u2010induced inflammation. Interestingly, in vivo, serum urate concentrations were inversely correlated to in vitro ISG expression upon stimulations with TLR ligands. These findings support a deficient IFN1 signalling in the presence of elevated serum urate concentrations, which could translate to increased susceptibility to infections.<\/jats:p>","DOI":"10.1111\/imm.13858","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T06:19:26Z","timestamp":1727849966000},"page":"100-112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Downregulation of type I interferon signalling pathway by urate in primary human <scp>PBMCs<\/scp>"],"prefix":"10.1111","volume":"174","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1185-8729","authenticated-orcid":false,"given":"Medeea","family":"Badii","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Iuliu Ha\u021bieganu University of Medicine and Pharmacy  Cluj\u2010Napoca Romania"},{"name":"Department of Internal Medicine and Research Institute for Medical Innovation Radboud University Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Nica","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Iuliu Ha\u021bieganu University of Medicine and Pharmacy  Cluj\u2010Napoca Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ancu\u021ba R.","family":"Straton","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Iuliu Ha\u021bieganu University of Medicine and Pharmacy  Cluj\u2010Napoca Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6963-1001","authenticated-orcid":false,"given":"Brenda","family":"Kischkel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Research Institute for Medical Innovation Radboud University Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orsolya","family":"Gaal","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Iuliu Ha\u021bieganu University of Medicine and Pharmacy  Cluj\u2010Napoca Romania"},{"name":"Department of Internal Medicine and Research Institute for Medical Innovation Radboud University Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgiana","family":"Cab\u0103u","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Iuliu Ha\u021bieganu University of Medicine and Pharmacy  Cluj\u2010Napoca Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2802-2239","authenticated-orcid":false,"given":"Viola","family":"Kl\u00fcck","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Research Institute for Medical Innovation Radboud University Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Hotea","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Iuliu Ha\u021bieganu University of Medicine and Pharmacy  Cluj\u2010Napoca Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"HINT Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5623-9008","authenticated-orcid":false,"given":"Boris","family":"Novakovic","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute and Department of Paediatrics University of Melbourne, Royal Children's Hospital  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Pamfil","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Iuliu Ha\u021bieganu University of Medicine and Pharmacy  Cluj\u2010Napoca Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8149-7722","authenticated-orcid":false,"given":"Simona","family":"Rednic","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Iuliu Ha\u021bieganu University of Medicine and Pharmacy  Cluj\u2010Napoca Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2421-6052","authenticated-orcid":false,"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Research Institute for Medical Innovation Radboud University Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radu A.","family":"Popp","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Iuliu Ha\u021bieganu University of Medicine and Pharmacy  Cluj\u2010Napoca Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6166-9830","authenticated-orcid":false,"given":"Leo A. B.","family":"Joosten","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Iuliu Ha\u021bieganu University of Medicine and Pharmacy  Cluj\u2010Napoca Romania"},{"name":"Department of Internal Medicine and Research Institute for Medical Innovation Radboud University Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3282-5627","authenticated-orcid":false,"given":"Tania O.","family":"Cri\u0219an","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Iuliu Ha\u021bieganu University of Medicine and Pharmacy  Cluj\u2010Napoca Romania"},{"name":"Department of Internal Medicine and Research Institute for Medical Innovation Radboud University Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000028"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176055"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0115-y"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0334-3"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20344"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1814"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056864"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206564"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1620910114"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2500"},{"issue":"7","key":"e_1_2_10_12_1","first-page":"3167","article-title":"Update on the epidemiology, genetics, and therapeutic options of hyperuricemia","volume":"12","author":"Li L","year":"2020","journal-title":"Am J Transl Res"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27198-4"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-021-02580-1"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41173"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110489"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181100"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.08.007"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3787"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2005.24.614"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031023"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01687-x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.09.016"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.03.013"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3581"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/1043-4666(93)90030-9"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.150.10.4687"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.02.006"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.02.003"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2016.25"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2024.105698"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1604"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.12.7823"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a021379"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.829877"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.633767"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(21)00401-X"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01588-5"},{"issue":"1","key":"e_1_2_10_39_1","first-page":"1","article-title":"Uric acid as a prognostic factor and critical marker of COVID\u201019","volume":"11","author":"Li G","year":"2021","journal-title":"Sci Rep"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-021-03616-3"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-017-1465-9"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2022.07.014"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi879"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.13858","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T03:16:55Z","timestamp":1734491815000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.13858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/imm.13858"],"URL":"https:\/\/doi.org\/10.1111\/imm.13858","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2023-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}