ArticleArthritis & rheumatology (Hoboken, N.J.)2015
Promotion of Inflammatory Arthritis by Interferon Regulatory Factor 5 in a Mouse Model.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Regulation of differentiation and generation of osteoclasts in rheumatoid arthritis.Frontiers in immunology · 2022Pooled it
- Pathogens in rheumatoid arthritis: epidemiological, mechanistic, and clinical insights.Biomarker research · 2026Review
- Leveraging cell-type specificity and similarity improves single-cell eQTL fine-mapping.Nature communications · 2026Article
- Genetic alternative splicing regulation mapping of cartilage and synovium reveals tissue-specific mechanisms of joint-related traits.Nature communications · 2026Article
- scTWAS: a powerful statistical framework for single-cell transcriptome-wide association studies.Nature communications · 2026Article
- Multilevel Exploration of Shared Genetic Architecture Between Primary Biliary Cholangitis and Four Autoimmune Diseases.Endocrine, metabolic & immune disorders drug targets · 2026Article
- Review
- Gout Risk Allele RegulatingInternational journal of molecular sciences · 2025Article
- scTWAS: A powerful statistical framework for single-cell transcriptome-wide association studies.Research square · 2025Article
- IRF5 Mediates Artery Inflammation in Salt-Sensitive Hypertension by Regulating STAT1 and STAT2 Phosphorylation to Increase ESM1 Transcription: Insights from Bioinformatics and Mechanistic Analysis.International journal of molecular sciences · 2025Article
- Interferon regulatory factor 5: a potential target for therapeutic intervention in inflammatory diseases.Frontiers in immunology · 2025Review
- TRIM21 regulation of IRF-mediated type I interferon signaling in systemic autoimmune diseases.Frontiers in immunology · 2025Review
- Citrullinated peptides as drug candidates for rheumatoid arthritis.Frontiers in immunology · 2025Review
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Emerging Landscape ofACS pharmacology & translational science · 2024Review
- Cell-specific gene networks and drivers in rheumatoid arthritis synovial tissues.Frontiers in immunology · 2024Article
- Targeting transcription factors for therapeutic benefit in rheumatoid arthritis.Frontiers in immunology · 2023Review
- Antiviral Innate Immune Responses in Autoimmunity: Receptors, Pathways, and Therapeutic Targeting.Biomedicines · 2022Review
- Defactinib inhibits PYK2 phosphorylation of IRF5 and reduces intestinal inflammation.Nature communications · 2021Article
- Myeloid cell-specific Irf5 deficiency stabilizes atherosclerotic plaques in ApoeMolecular metabolism · 2021Article
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
objectivePolymorphisms in the transcription factor interferon regulatory factor 5 (IRF5) are associated with an increased risk of developing rheumatoid arthritis (RA). This study was undertaken to determine the role of IRF5 in a mouse model of arthritis development.
methodsK/BxN serum-transfer arthritis was induced in mice deficient in IRF5, or lacking IRF5 only in myeloid cells, and arthritis severity was evaluated. K/BxN arthritis was also induced in mice deficient in TRIF, Toll-like receptor 2 (TLR2), TLR3, TLR4, and TLR7 to determine the pathways through which IRF5 might promote arthritis. In vitro studies were performed to determine the role of IRF5 in interleukin-1 (IL-1) receptor and TLR signaling.
resultsArthritis severity was reduced in IRF5-deficient, TRIF-deficient, TLR3-deficient, and TLR7-deficient mice. The expression of multiple genes regulating neutrophil recruitment or function and bioactive IL-1β formation was reduced in the joints during active arthritis in IRF5-deficient mice. In vitro studies showed that TLR7 and the TRIF-dependent TLR3 pathway induce proinflammatory cytokine production in disease-relevant cell types in an IRF5-dependent manner.
conclusionOur findings indicate that IRF5 contributes to disease pathogenesis in inflammatory arthritis. This is likely due at least in part to the role of IRF5 in mediating proinflammatory cytokine production downstream of TLR7 and TLR3. Since TLR7 and TLR3 are both RNA-sensing TLRs, this suggests that endogenous RNA ligands present in the inflamed joint promote arthritis development. These findings may be relevant to human RA, since RNA capable of activating TLR7 and TLR3 is present in synovial fluid and TLR7 and TLR3 are up-regulated in the joints of RA patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.