The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Negative regulation of Toll-like-receptor signaling by IRF-4
Open accessAbstract
The recognition of microbial components by Toll-like receptors (TLRs) is an event central to the activation of innate and adaptive immune systems. TLR activation triggers the induction of downstream target genes, wherein the TLR-interacting adaptor molecule MyD88 recruits various signaling molecules and transcription factors. Two members of the IFN regulatory factor (IRF) family of transcription factors, IRF-5 and IRF-7, interact with MyD88 and induce proinflammatory cytokines and type I IFNs, respectively. Here, we show that IRF-4 also interacts with MyD88 and acts as a negative regulator of TLR signaling. IRF-4 mRNA is induced by TLR activation, and IRF-4 competes with IRF-5, but not with IRF-7, for MyD88 interaction. The TLR-dependent induction of proinflammatory cytokines is markedly enhanced in peritoneal macrophages from mice deficient in the Irf4 gene, whereas the induction is inhibited by the ectopic expression of IRF-4 in a macrophage cell line. The critical function of IRF-4 in TLR signaling in vivo is underscored by the observation that Irf4 -deficient mice show hypersensitivity to DNA-induced shock, with elevated serum proinflammatory cytokine levels. This study may provide an insight into the complex regulatory mechanisms of MyD88 signaling by IRFs.
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Cites
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Self-citationNegative regulation of Toll-like receptor-mediated immune responses
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Self-citationReview: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells
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Cited by
The IRF Family Transcription Factors in Immunity and Oncogenesis
Tamura, T., Yanai, H., Savitsky, D., & Taniguchi, T. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090400 · Cited by 1,259
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TAM Receptors Are Pleiotropic Inhibitors of the Innate Immune Response
Rothlin, C. V., Ghosh, S., Zuniga, E. I., Oldstone, M. B. A., & Lemke, G. (2007) · Cell · doi:10.1016/j.cell.2007.10.034 · Cited by 1,055
TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages
Martinon, F., Chen, X., Lee, A.-H., & Glimcher, L. H. (2010) · Nature Immunology · doi:10.1038/ni.1857 · Cited by 996
Metadata
- Authors
- Negishi, H., Ohba, Y., Yanai, H., Takaoka, A., Honma, K., Yui, K., Matsuyama, T., Taniguchi, T., & Honda, K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2005-10-19
- Volume
- 102
- Issue
- 44
- Pages
- 15989-15994
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2056502408
- Cited by
- 405
- References
- 10
- FWCI
- 6.98
- Type
- journal article
- Language
- en
- Open access
- green
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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