{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:14:17Z","timestamp":1790493257734,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2012,4,1]],"date-time":"2012-04-01T00:00:00Z","timestamp":1333238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Genetic polymorphisms of IFN regulatory factor 5 (IRF5) are associated with an increased risk of lupus in humans. In this study, we examined the role of IRF5 in the pathogenesis of pristane-induced lupus in mice. The pathological response to pristane in IRF5\u2212\/\u2212 mice shared many features with type I IFN receptor (IFNAR)\u2212\/\u2212 and TLR7\u2212\/\u2212 mice: production of anti-Sm\/RNP autoantibodies, glomerulonephritis, generation of Ly6Chi monocytes, and IFN-I production all were greatly attenuated. Lymphocyte activation following pristane injection was greatly diminished in IRF5\u2212\/\u2212 mice, and Th cell differentiation was deviated from Th1 in wild-type mice toward Th2 in IRF5\u2212\/\u2212 mice. Th cell development was skewed similarly in TLR7\u2212\/\u2212 or IFNAR\u2212\/\u2212 mice, suggesting that IRF5 alters T cell activation and differentiation by affecting cytokine production. Indeed, production of IFN-I, IL-12, and IL-23 in response to pristane was markedly decreased, whereas IL-4 increased. Unexpectedly, plasmacytoid dendritic cells (pDC) were not recruited to the site of inflammation in IRF5\u2212\/\u2212 or MyD88\u2212\/\u2212 mice, but were recruited normally in IFNAR\u2212\/\u2212 and TLR7\u2212\/\u2212 mice. In striking contrast to wild-type mice, pristane did not stimulate local expression of CCL19 and CCL21 in IRF5\u2212\/\u2212 mice, suggesting that IRF5 regulates chemokine-mediated pDC migration independently of its effects on IFN-I. Collectively, these data indicate that altered production of IFN-I and other cytokines in IRF5\u2212\/\u2212 mice prevents pristane from inducing lupus pathology by broadly affecting T and B lymphocyte activation\/differentiation. Additionally, we uncovered a new, IFN-I\u2013independent role of IRF5 in regulating chemokines involved in the homing of pDCs and certain lymphocyte subsets.<\/jats:p>","DOI":"10.4049\/jimmunol.1103113","type":"journal-article","created":{"date-parts":[[2012,3,15]],"date-time":"2012-03-15T07:33:41Z","timestamp":1331796821000},"page":"4113-4121","source":"Crossref","is-referenced-by-count":52,"title":["Pleiotropic IFN-Dependent and -Independent Effects of IRF5 on the Pathogenesis of Experimental Lupus"],"prefix":"10.1093","volume":"188","author":[{"given":"Yuan","family":"Xu","sequence":"first","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville , FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pui Y","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville , FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville , FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyang","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville , FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhong","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville , FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina C","family":"Nacionales","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville , FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton E","family":"Mathews","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyle L","family":"Moldawer","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Wu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Satoh","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville , FL 32610"},{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Westley H","family":"Reeves","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville , FL 32610"},{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,4,15]]},"reference":[{"key":"2025032410040961300_r1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nature03308","article-title":"Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors","volume":"434","author":"Takaoka","year":"2005","journal-title":"Nature"},{"key":"2025032410040961300_r2","doi-asserted-by":"crossref","first-page":"23382","DOI":"10.1074\/jbc.M101216200","article-title":"Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes","volume":"276","author":"Barnes","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2025032410040961300_r3","doi-asserted-by":"crossref","first-page":"17005","DOI":"10.1074\/jbc.M412584200","article-title":"The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling","volume":"280","author":"Schoenemeyer","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2025032410040961300_r4","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1073\/pnas.0712295105","article-title":"A cell-type-specific requirement for IFN regulatory factor 5 (IRF5) in Fas-induced apoptosis","volume":"105","author":"Couzinet","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032410040961300_r5","doi-asserted-by":"crossref","first-page":"4664","DOI":"10.1073\/pnas.0911193107","article-title":"Critical role of IRF-5 in regulation of B-cell differentiation","volume":"107","author":"Lien","year":"2010","journal-title":"Proc. Natl. Acad. Sci. 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Multiple isoforms with distinct cell type-specific expression, localization, regulation, and function","volume":"280","author":"Mancl","year":"2005","journal-title":"J. Biol. 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