{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T10:18:12Z","timestamp":1783937892439,"version":"3.55.0"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Uveitis accounts for up to 25% of global legal blindness and involves intraocular inflammation, classifed as infectious or non-infectious. Its complex pathophysiology includes dysregulated cytokines, particularly interferons (IFNs). However, the global signature of type I, II, and III interferon-regulated genes (Interferome) remains largely uncharacterized in uveitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we conducted an integrative systems biology analysis of blood transcriptome data from 169 non-infectious uveitis patients (56 isolated uveitis, 113 systemic disease-associated uveitis) and 82 healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Modular co-expression analysis identified distinct cytokine signaling networks, emphasizing interleukin and interferon pathways. A meta-analysis revealed 110 differentially expressed genes (metaDEGs) in isolated uveitis and 91 in systemic disease-associated uveitis, predominantly linked to immune responses. The Interferome database confirmed a predominance of type I and II IFN signatures in both groups. Pathway enrichment analysis highlighted inflammatory responses, including cytokine production (IL-8, IL1-\u03b2, IFN-\u03b3, \u03b2, and \u03b1) and toll-like receptor signaling (TLR4, TLR7, TLR8, CD180). Principal component analysis emphasized the IFN signature\u2019s discriminative power, particularly in systemic disease-associated uveitis. Machine learning identified IFN-associated genes as robust predictors, while linear discriminant analysis pinpointed CCR2, CD180, GAPT, and PTGS2 as key risk factors in isolated uveitis and CA1, SIAH2, and PGS in systemic disease-associated uveitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings highlight IFN-driven imune dysregulation and potential molecular targets for precision therapies in uveitis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1509805","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T05:22:13Z","timestamp":1744176133000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrative immunology identified interferome signatures in uveitis and systemic disease-associated uveitis"],"prefix":"10.3389","volume":"16","author":[{"given":"Danielle Dias","family":"Munhoz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennyson Leandro M.","family":"Fonseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor Salerno","family":"Filgueiras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haroldo Dutra","family":"Dias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helder I.","family":"Nakaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Jurisica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans D.","family":"Ochs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena F.","family":"Schimke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Vicente","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otavio","family":"Cabral-Marques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmed.2022-0046","article-title":"Inflammatory eye disease: An overview of clinical presentation and management","volume":"22","author":"Miller","year":"2022","journal-title":"Clin Med (Lond)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1997.01100150522013","article-title":"Immunologic mechanisms of uveitis. 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