{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T18:54:53Z","timestamp":1777316093097,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:00:00Z","timestamp":1760227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Romanian Ministry of European Funds","award":["P_37_762"],"award-info":[{"award-number":["P_37_762"]}]},{"name":"Romanian Ministry of European Funds","award":["MySMIS 103587"],"award-info":[{"award-number":["MySMIS 103587"]}]},{"name":"Romania\u2019s National Recovery and Resilience Plan grant of the Romanian Ministry of Investments and European Projects","award":["PNRR-III-C9-2022-I8"],"award-info":[{"award-number":["PNRR-III-C9-2022-I8"]}]},{"name":"Romania\u2019s National Recovery and Resilience Plan grant of the Romanian Ministry of Investments and European Projects","award":["CF 85\/15.11.2022"],"award-info":[{"award-number":["CF 85\/15.11.2022"]}]},{"name":"grant for doctoral research of the University of Medicine and Pharmacy \u201cIuliu Ha\u021bieganu\u201d","award":["2461\/51"],"award-info":[{"award-number":["2461\/51"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Interferon Regulatory Factor 5 plays an important role in the regulation of innate immune responses by amplifying the Nuclear Factor \u03baB response, which is critical in gout inflammation. Furthermore, the rs4728141 polymorphism C allele was associated with both increased IRF5 expression and susceptibility to gout. We examine the association between rs4728141 and cytokine production in response to various Toll-Like Receptor ligands and describe the transcriptomic and proteomic changes observed in patients with gout and controls in relation to this polymorphism. We examine the transcriptome of freshly isolated peripheral blood mononuclear cells (PBMCs) from 93 normouricemic donors and 63 gout patients as well as serum inflammatory proteome in 197 control and 195 gout samples. Stimulation experiments of freshly isolated human PBMCs were performed over 24 h, followed by RNA-sequencing in gout patients and cytokine production measurement by ELISA in normouricemic donors and gout patients. The rs4728141 C allele was associated with increased IL-1\u03b2 expression in unstimulated PBMCs of controls, but not in gout. No association between the polymorphism and serum inflammatory proteome was found. As expected, an increased IRF5 expression was observed in stimulated PBMCs of rs4728141 C allele carriers in response to several stimulations. Interestingly, IL-1\u03b2 production was specifically enhanced in association to the rs4728141 C allele when cells were stimulated with palmitate with or without monosodium urate crystals. This pattern of cytokine production shows a functional impact of rs4728141 in gout through altered IL-1\u03b2 production.<\/jats:p>","DOI":"10.3390\/ijms26209930","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T16:13:03Z","timestamp":1760717583000},"page":"9930","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gout Risk Allele Regulating IRF5 Expression Is Associated with Enhanced IL-1\u03b2 Production in Response to Palmitate and Monosodium Urate Crystals"],"prefix":"10.3390","volume":"26","author":[{"given":"Valentin","family":"Nica","sequence":"first","affiliation":[{"name":"Department of Translational Immunology, Medfuture Institute for Biomedical Research, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"},{"name":"Department of Medical Genetics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orsolya","family":"Gaal","sequence":"additional","affiliation":[{"name":"Department of Translational Immunology, Medfuture Institute for Biomedical Research, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"},{"name":"Department of Medical Genetics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"},{"name":"Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Medeea","family":"Badii","sequence":"additional","affiliation":[{"name":"Department of Translational Immunology, Medfuture Institute for Biomedical Research, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"},{"name":"Department of Medical Genetics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"},{"name":"Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgiana","family":"Cab\u0103u","sequence":"additional","affiliation":[{"name":"Department of Translational Immunology, Medfuture Institute for Biomedical Research, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"},{"name":"Department of Medical Genetics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9297-9871","authenticated-orcid":false,"given":"Andreea-Manuela","family":"Mirea","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioana","family":"Hotea","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Clinicilor 2-4, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Pamfil","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Clinicilor 2-4, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Rednic","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Clinicilor 2-4, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radu A.","family":"Popp","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania O.","family":"Cri\u0219an","sequence":"additional","affiliation":[{"name":"Department of Translational Immunology, Medfuture Institute for Biomedical Research, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"},{"name":"Department of Medical Genetics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"},{"name":"Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6166-9830","authenticated-orcid":false,"given":"Leo A. B.","family":"Joosten","sequence":"additional","affiliation":[{"name":"Department of Translational Immunology, Medfuture Institute for Biomedical Research, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"},{"name":"Department of Medical Genetics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Str. Pasteur Nr. 6, 400349 Cluj-Napoca, Romania"},{"name":"Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"HINT Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41572-019-0115-y","article-title":"Gout","volume":"5","author":"Dalbeth","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1136\/annrheumdis-2014-206397","article-title":"Urate crystal deposition in asymptomatic hyperuricaemia and symptomatic gout: A dual energy CT study","volume":"74","author":"Dalbeth","year":"2015","journal-title":"Ann. Rheum. 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