Trial reportThe Journal of clinical investigation2020
Inhibition of IRF5 hyperactivation protects from lupus onset and severity.
Trial report in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Meta-analyses identify DNA methylation associated with kidney function and damage.Nature communications · 2021Pooled it
- The SLC15A4-TASL complex is essential for lupus development in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Pharmacological targeting of IRF4 as a therapeutic strategy for multiple myeloma.Nature chemical biology · 2026Article
- scTWAS: a powerful statistical framework for single-cell transcriptome-wide association studies.Nature communications · 2026Article
- Interferon regulatory factor 5 involves the pathogenesis of emphysema through NLRP3 and Ly6C expressing cells.Experimental & molecular medicine · 2026Article
- Review
- Article
- Keratinocyte VISTA attenuates UV light-induced skin injury by suppressing cutaneous type I interferon (IFN-I) response.bioRxiv : the preprint server for biology · 2025Article
- scTWAS: A powerful statistical framework for single-cell transcriptome-wide association studies.Research square · 2025Article
- Interferon Regulator Factor 5: A Novel Inflammatory Marker and Promising Therapeutic Target in Ulcerative Colitis.Biomedicines · 2025Article
- TLR-induced STK25 activation promotes IRF5-mediated inflammation.Life science alliance · 2025Article
- Dendritic cell heterogeneity and its role in connective tissue diseases.Inflammation and regeneration · 2025Review
- What's atypical about human B cells after allogeneic stem cell transplantation?Journal of leukocyte biology · 2025Review
- Article
- IRF5 Controls Plasma Cell Generation and Antibody Production via Distinct Mechanisms Depending on the Antigenic Trigger.Immunology · 2025Article
- An overview on Sjögren's syndrome and systemic lupus erythematosus' genetics.Toxicology research · 2025Review
- The TLR7/9 adaptors TASL and TASL2 mediate IRF5-dependent antiviral responses and autoimmunity in mouse.Nature communications · 2025Article
- B cell subpopulations and their role in the pathogenesis of primary Sjögren's syndrome: insights from single-cell RNA sequencing.Frontiers in immunology · 2025Article
- Interferon regulatory factor 5: a potential target for therapeutic intervention in inflammatory diseases.Frontiers in immunology · 2025Review
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
Corrections and comments
- Commented on by
Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
The transcription factor IFN regulatory factor 5 (IRF5) is a central mediator of innate and adaptive immunity. Genetic variations within IRF5 are associated with a risk of systemic lupus erythematosus (SLE), and mice lacking Irf5 are protected from lupus onset and severity, but how IRF5 functions in the context of SLE disease progression remains unclear. Using the NZB/W F1 model of murine lupus, we show that murine IRF5 becomes hyperactivated before clinical onset. In patients with SLE, IRF5 hyperactivation correlated with dsDNA titers. To test whether IRF5 hyperactivation is a targetable function, we developed inhibitors that are cell permeable, nontoxic, and selectively bind to the inactive IRF5 monomer. Preclinical treatment of NZB/W F1 mice with an inhibitor attenuated lupus pathology by reducing serum antinuclear autoantibodies, dsDNA titers, and the number of circulating plasma cells, which alleviated kidney pathology and improved survival. Clinical treatment of MRL/lpr and pristane-induced lupus mice with an inhibitor led to significant reductions in dsDNA levels and improved survival. In ex vivo human studies, the inhibitor blocked SLE serum-induced IRF5 activation and reversed basal IRF5 hyperactivation in SLE immune cells. We believe this study provides the first in vivo clinical support for treating patients with SLE with an IRF5 inhibitor.
Indexed as
Identifiers
What OpenQuestion holds
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.