ArticleJournal of immunology (Baltimore, Md. : 1950)2015
IRF5 deficiency ameliorates lupus but promotes atherosclerosis and metabolic dysfunction in a mouse model of lupus-associated atherosclerosis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Meta-analysis of genome-wide association study identifies FBN2 as a novel locus associated with systemic lupus erythematosus in Thai population.Arthritis research & therapy · 2020Pooled it
- Inhibition of IRF5 hyperactivation protects from lupus onset and severity.The Journal of clinical investigation · 2020Trial
- The role of interferon regulatory factors in atherosclerosis: from cell type-specific mechanisms to therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- IRF5 Controls Plasma Cell Generation and Antibody Production via Distinct Mechanisms Depending on the Antigenic Trigger.Immunology · 2025Article
- The role of interferon regulatory factors in atherosclerosis.Frontiers in cardiovascular medicine · 2025Review
- Precision medicine in systemic lupus erythematosus.Nature reviews. Rheumatology · 2023Review
- A phospho-tyrosine-based signaling module using SPOP, CSK, and LYN controls TLR-induced IRF activity.Science advances · 2022Article
- Disturbances of circadian profile and blood pressure control in patients with systemic lupus erythematosus without overt heart disease.Postepy dermatologii i alergologii · 2022Article
- Myeloid cell-specific Irf5 deficiency stabilizes atherosclerotic plaques in ApoeMolecular metabolism · 2021Article
- Monoallelic IRF5 deficiency in B cells prevents murine lupus.JCI insight · 2021Article
- Genetic and chemical inhibition of IRF5 suppresses pre-existing mouse lupus-like disease.Nature communications · 2021Article
- The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis.Molecular therapy. Nucleic acids · 2021Article
- Interferon Regulatory Factor 5 (Biomolecules · 2021Article
- Myeloid Cell-Intrinsic IRF5 Promotes T Cell Responses through Multiple Distinct Checkpoints In Vivo, andJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Coordination between innate immune cells, type I IFNs and IRF5 drives SLE pathogenesis.Cytokine · 2020Review
- T Cell-Intrinsic IRF5 Regulates T Cell Signaling, Migration, and Differentiation and Promotes Intestinal Inflammation.Cell reports · 2020Article
- The Role of Toll-like Receptors in Atherothrombotic Cardiovascular Disease.ACS pharmacology & translational science · 2020Review
- Exacerbated Imiquimod-Induced Psoriasis-Like Skin Inflammation in IRF5-Deficient Mice.International journal of molecular sciences · 2020Article
- Inhibition of IRF5 cellular activity with cell-penetrating peptides that target homodimerization.Science advances · 2020Article
- Article
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Premature atherosclerosis is a severe complication of lupus and other systemic autoimmune disorders. Gain-of-function polymorphisms in IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing lupus, and IRF5 deficiency in lupus mouse models ameliorates disease. However, whether IRF5 deficiency also protects against atherosclerosis development in lupus is not known. In this study, we addressed this question using the gld.apoE(-/-) mouse model. IRF5 deficiency markedly reduced lupus disease severity. Unexpectedly, despite the reduction in systemic immune activation, IRF5-deficient mice developed increased atherosclerosis and also exhibited metabolic dysregulation characterized by hyperlipidemia, increased adiposity, and insulin resistance. Levels of the atheroprotective cytokine IL-10 were reduced in aortae of IRF5-deficient mice, and in vitro studies demonstrated that IRF5 is required for IL-10 production downstream of TLR7 and TLR9 signaling in multiple immune cell types. Chimera studies showed that IRF5 deficiency in bone marrow-derived cells prevents lupus development and contributes in part to the increased atherosclerosis. Notably, IRF5 deficiency in non-bone marrow-derived cells also contributes to the increased atherosclerosis through the generation of hyperlipidemia and increased adiposity. Together, our results reveal a protective role for IRF5 in lupus-associated atherosclerosis that is mediated through the effects of IRF5 in both immune and nonimmune cells. These findings have implications for the proposed targeting of IRF5 in the treatment of autoimmune disease as global IRF5 inhibition may exacerbate cardiovascular disease in these 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.