Cited by 411interferon and immune responsesImmune Response and InflammationImmunotherapy and Immune Responses

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The Interferon Regulatory Factor, IRF5, Is a Central Mediator of Toll-like Receptor 7 Signaling

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Schoenemeyer, Annett, Barnes, Betsy J., Mancl, Margo.E., Latz, Eicke, Goutagny, Nadege, Pitha, Paula M., Fitzgerald, Katherine A., Golenbock, Douglas T.·2005·Journal of Biological Chemistry

DOI 10.1074/jbc.m412584200

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Abstract

Interferon regulatory factors (IRFs) are critical components of virus-induced immune activation and type I interferon regulation. IRF3 and IRF7 are activated in response to a variety of viruses or after engagement of Toll-like receptor (TLR) 3 and TLR4 by double-stranded RNA and lipopolysaccharide, respectively. The activation of IRF5, is much more restricted. Here we show that in contrast to IRF3 and IRF7, IRF5 is not a target of the TLR3 signaling pathway but is activated by TLR7 or TLR8 signaling. We also demonstrate that MyD88, interleukin 1 receptor-associated kinase 1, and tumor necrosis factor receptor-associated factor 6 are required for the activation of IRF5 and IRF7 in the TLR7 signaling pathway. Moreover, ectopic expression of IRF5 enabled type I interferon production in response to TLR7 signaling, whereas knockdown of IRF5 by small interfering RNA reduced type I interferon induction in response to the TLR7 ligand, R-848. IRF5 and IRF7, therefore, emerge from these studies as critical mediators of TLR7 signaling.

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Authors: Schoenemeyer, A., Barnes, B. J., Mancl, M. E., Latz, E., Goutagny, N., Pitha, P. M., Fitzgerald, K. A., & Golenbock, D. T.
Affiliations: University of Massachusetts Chan Medical School (US)
Johns Hopkins University (US)
Corresponding author: Fitzgerald, Katherine A.
Golenbock, Douglas T.
ORCID: Barnes, Betsy J.
Latz, Eicke
Fitzgerald, Katherine A.
Golenbock, Douglas T.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2005-04
Volume: 280
Issue: 17
Pages: 17005-17012
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m412584200
OpenAlex: W2040706148
Cited by: 411
References: 72
Citations by year: 2026: 7 · 2025: 8 · 2024: 16 · 2023: 16 · 2022: 11 · 2021: 13 · 2020: 16 · 2019: 21 · 2018: 23 · 2017: 25 · 2016: 11 · 2015: 14 · 2014: 25 · 2013: 17 · 2012: 20
FWCI: 11.11
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 5677 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
eScholarship@UMassChan (submittedVersion)
Funders: National Cancer Institute (R01A1/CA19737-19A1)
National Institute of General Medical Sciences (GM 54060)
National Institute of Allergy and Infectious Diseases (AI-52455, AI 49309, R01AI049309)
Topics: Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: IRF5, IRF7, TLR7, TLR8, TLR7 signaling, type I interferon, MyD88, TRAF6, IRAK1, IRF3, interferon regulatory factors, R848, innate immunity
MeSH terms: Antigens, Differentiation, Biological Assay, Cell Line, DNA-Binding Proteins, Dose-Response Relationship, Drug, Glutathione Transferase, Humans, Interferon Type I, Ligands, Lipopolysaccharides, Membrane Glycoproteins, Models, Biological, Phosphorylation, Receptors, Cell Surface, Receptors, Immunologic, Recombinant Fusion Proteins, RNA, Double-Stranded, Time Factors, Transcription Factors, Transfection, Signal Transduction, Genes, Reporter, Electroporation, Microscopy, Confocal, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, RNA, Small Interfering, Adaptor Proteins, Signal Transducing, Interferon Regulatory Factors, Interferon Regulatory Factor-3, Interferon Regulatory Factor-7, Toll-Like Receptors, Toll-Like Receptor 3, Toll-Like Receptor 4, Toll-Like Receptor 7, Toll-Like Receptor 8, Myeloid Differentiation Factor 88

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The Interferon Regulatory Factor, IRF5, Is a Central Mediator of Toll-like Receptor 7 Signaling

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