{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:56:53Z","timestamp":1790474213152,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"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. Lupus"],"abstract":"<jats:sec><jats:title>Background\/Purpose<\/jats:title><jats:p>Cutaneous lupus erythematosus (CLE) affects up to 70% of patients with systemic lupus erythematosus (SLE), and type I interferons (IFNs) are important promoters of SLE and CLE. Our previous work identified IFN-kappa (IFN-\u03ba), a keratinocyte-produced type I IFN, as upregulated in non-lesional and lesional lupus skin and as a critical regulator for enhanced UVB-mediated cell death in SLE keratinocytes. Importantly, the molecular mechanisms governing regulation of IFN-\u03ba expression have been relatively unexplored. Thus, this study sought to identify critical regulators of IFN-\u03ba and identified a novel role for IFN-beta (IFN-\u03b2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human N\/TERT keratinocytes were treated with the RNA mimic poly (I:C) or 50\u2005mJ\/cm<jats:sup>2<\/jats:sup> ultraviolet B (UVB), followed by mRNA expression quantification by RT-qPCR in the presence or absence neutralizing antibody to the type I IFN receptor (IFNAR). IFNB and <jats:italic>STAT1<\/jats:italic> knockout (KO) keratinocytes were generated using CRISPR\/Cas9.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Time courses of poly(I:C) and UVB treatment revealed a differential expression of <jats:italic>IFNB<\/jats:italic>, which was upregulated between 3 and 6\u2005h and <jats:italic>IFNK<\/jats:italic>, which was upregulated 24\u2005h after stimulation. Intriguingly, only <jats:italic>IFNK<\/jats:italic> expression was substantially abrogated by neutralizing antibodies to IFNAR, suggesting that <jats:italic>IFNK<\/jats:italic> upregulation required type I IFN signaling for induction. Indeed, deletion of <jats:italic>IFNB<\/jats:italic> abrogated <jats:italic>IFNK expression<\/jats:italic>. Further exploration confirmed a role for type I IFN-triggered STAT1 activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Collectively, our work describes a novel mechanistic paradigm in keratinocytes in which initial IFN-\u03ba induction in response to poly(I:C) and UVB is IFN\u03b21-dependent, thus describing <jats:italic>IFNK<\/jats:italic> as both an IFN gene and an interferon-stimulated gene.<\/jats:p><\/jats:sec>","DOI":"10.3389\/flupu.2024.1359714","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T04:29:52Z","timestamp":1710822592000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["A critical role for IFN-\u03b2 signaling for IFN-\u03ba induction in keratinocytes"],"prefix":"10.3389","volume":"2","author":[{"given":"Bin","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Musai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee Sun","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace A.","family":"Hile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Swindell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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