ArticlePloS one2014
Interferon regulatory factor-5 deficiency ameliorates disease severity in the MRL/lpr mouse model of lupus in the absence of a mutation in DOCK2.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- 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
- An essential role for TASL in mouse autoimmune pathogenesis and Toll-like receptor signaling.Nature communications · 2025Article
- IRF5 mediates adaptive immunity via altered glutamine metabolism, mTORC1 signaling and post-transcriptional regulation following T cell receptor activation.bioRxiv : the preprint server for biology · 2024Article
- Genetic polymorphisms in genes involved in the type I interferon system (STAT4 and IRF5): association with Asian SLE patients.Clinical rheumatology · 2024Review
- Unraveling the Link between Interferon-α and Systemic Lupus Erythematosus: From the Molecular Mechanisms to Target Therapies.International journal of molecular sciences · 2022Review
- A phospho-tyrosine-based signaling module using SPOP, CSK, and LYN controls TLR-induced IRF activity.Science advances · 2022Article
- The gene silencing of IRF5 and BLYSS effectively modulates the outcome of experimental lupus nephritis.Molecular therapy. Nucleic acids · 2021Article
- Hyper-metabolic B cells in the spleens of old mice make antibodies with autoimmune specificities.Immunity & ageing : I & A · 2021Article
- HMGB1-C1q complexes regulate macrophage function by switching between leukotriene and specialized proresolving mediator biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Genetic Versus Non-genetic Drivers of SLE: Implications of IRF5 Dysregulation in Both Roads Leading to SLE.Current rheumatology reports · 2019Review
- Regulating IRFs in IFN Driven Disease.Frontiers in immunology · 2019Review
- B Cell Defects Observed inJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- Regulation of age-associated B cells by IRF5 in systemic autoimmunity.Nature immunology · 2018Article
- Type I interferon in rheumatic diseases.Nature reviews. Rheumatology · 2018Review
- Lineage-Specific Functionality of an Interferon Regulatory Factor 5 Lupus Risk Haplotype: Lack of B Cell Intrinsic Effects.Frontiers in immunology · 2018Article
- Plasma Cell Differentiation Pathways in Systemic Lupus Erythematosus.Frontiers in immunology · 2018Review
- Follicular Dendritic Cell Activation by TLR Ligands Promotes Autoreactive B Cell Responses.Immunity · 2017Article
- B Cell-Intrinsic Role for IRF5 in TLR9/BCR-Induced Human B Cell Activation, Proliferation, and Plasmablast Differentiation.Frontiers in immunology · 2017Article
- Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Activates Type I Interferon Signals in Lupus Nephritis.BioMed research international · 2017Article
- IRF5 deficiency ameliorates lupus but promotes atherosclerosis and metabolic dysfunction in a mouse model of lupus-associated atherosclerosis.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Interferon regulatory factor 5 (IRF5) polymorphisms are strongly associated with an increased risk of developing the autoimmune disease systemic lupus erythematosus. In mouse lupus models, IRF5-deficiency was shown to reduce disease severity consistent with an important role for IRF5 in disease pathogenesis. However these mouse studies were confounded by the recent demonstration that the IRF5 knockout mouse line contained a loss-of-function mutation in the dedicator of cytokinesis 2 (DOCK2) gene. As DOCK2 regulates lymphocyte trafficking and Toll-like receptor signaling, this raised the possibility that some of the protective effects attributed to IRF5 deficiency in the mouse lupus models may instead have been due to DOCK2 deficiency. We have therefore here evaluated the effect of IRF5-deficiency in the MRL/lpr mouse lupus model in the absence of the DOCK2 mutation. We find that IRF5-deficient (IRF5-/-) MRL/lpr mice develop much less severe disease than their IRF5-sufficient (IRF5+/+) littermates. Despite markedly lower serum levels of anti-nuclear autoantibodies and reduced total splenocyte and CD4+ T cell numbers, IRF5-/- MRL/lpr mice have similar numbers of all splenic B cell subsets compared to IRF5+/+ MRL/lpr mice, suggesting that IRF5 is not involved in B cell development up to the mature B cell stage. However, IRF5-/- MRL/lpr mice have greatly reduced numbers of spleen plasmablasts and bone marrow plasma cells. Serum levels of B lymphocyte stimulator (BLyS) were markedly elevated in the MRL/lpr mice but no effect of IRF5 on serum BLyS levels was seen. Overall our data demonstrate that IRF5 contributes to disease pathogenesis in the MRL/lpr lupus model and that this is due, at least in part, to the role of IRF5 in plasma cell formation. Our data also suggest that combined therapy targeting both IRF5 and BLyS might be a particularly effective therapeutic approach in lupus.
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