{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:28:10Z","timestamp":1788672490268,"version":"build-2803163510"},"reference-count":418,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Type I interferons (IFN-I) are pivotal effectors of innate immunity and constitute a central axis of host defense against pathogens. Sensing of exogenous or endogenous nucleic acids by pattern-recognition receptors\u2014exemplified by Toll-like receptors\u2014triggers transcriptional induction of IFN-I. Engagement of the heterodimeric IFN-I receptor on nucleated cells reprograms cellular states via canonical Janus kinase\u2013signal transducer and activator of transcription (JAK\u2013STAT) signaling as well as STAT-independent, noncanonical pathways. This axis is tempered by multilayered regulatory mechanisms, including epigenetic remodeling, and important aspects remain incompletely defined. Dysregulation of IFN-I activity underlies diverse autoimmune disorders, notably systemic lupus erythematosus, wherein IFN-responsive gene signatures stratify disease endotypes, reflect disease activity trajectories, and predict therapeutic responsiveness. In recent years, therapeutic strategies targeting this pathway are now available: anti-IFN-I receptor therapy for systemic lupus erythematosus (SLE) and JAK inhibition for rheumatoid arthritis (RA) and giant cell arteritis (GCA). Altogether, a refined understanding of the IFN-I axis furnishes a pragmatic framework for patient stratification, response prediction, and mechanism-informed therapy design across immune-mediated diseases.<\/jats:p>","DOI":"10.3390\/biom15111586","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T10:56:47Z","timestamp":1762945007000},"page":"1586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Type I Interferon Axis in Systemic Autoimmune Diseases: From Molecular Pathways to Targeted Therapy"],"prefix":"10.3390","volume":"15","author":[{"given":"Ryuhei","family":"Ishihara","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1089-5296","authenticated-orcid":false,"given":"Ryu","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayu","family":"Shiomi","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"},{"name":"Department of Rheumatology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki 660-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0033-1757","authenticated-orcid":false,"given":"Masao","family":"Katsushima","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8576-5816","authenticated-orcid":false,"given":"Kazuo","family":"Fukumoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motomu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102430","DOI":"10.1016\/j.coi.2024.102430","article-title":"Type III interferons in innate and adaptive immunity in the respiratory tract","volume":"87","author":"Piperakis","year":"2024","journal-title":"Curr. 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