File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors

TitleIntegral role of IRF-5 in the gene induction programme activated by Toll-like receptors
Authors
Issue Date2005
Citation
Nature, 2005, v. 434, n. 7030, p. 243-249 How to Cite?
AbstractThe activation of Toll-like receptors (TLRs) is central to innate and adaptive immunity1-3. All TLRs use the adaptor MyD88 for signalling4, but the mechanisms underlying the MyD88-mediated gene induction programme are as yet not fully under-stood. Here, we demonstrate that the transcription factor IRF-5 is generally involved downstream of the TLR-MyD88 signalling pathway for gene induction of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-12 and tumour-necrosis factor-α. In haematopoietic cells from mice deficient in the Irf5 gene (Irf5-/- mice), the induction of these cytokines by various TLR ligands is severely impaired, whereas interferon-α induction is normal. We also provide evidence that IRF-5 interacts with and is activated by MyD88 and TRAF6, and that TLR activation results in the nuclear translocation of IRF-5 to activate cytokine gene transcription. Consistently, Irf5-/- mice show resistance to lethal shock induced by either unmethylated DNA or lipopolysaccharide, which correlates with a marked decrease in the serum levels of proinflammatory cytokines. Thus, our study identifies IRF-5 as a new, principal downstream regulator of the TLR-MyD88 signalling pathway and a potential target of therapeutic intervention to control harmful immune responses.
Persistent Identifierhttp://hdl.handle.net/10722/291691
ISSN
2023 Impact Factor: 50.5
2023 SCImago Journal Rankings: 18.509
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTakaoka, Akinori-
dc.contributor.authorYanai, Hideyuki-
dc.contributor.authorKondo, Seiji-
dc.contributor.authorDuncan, Gordon-
dc.contributor.authorNegishi, Hideo-
dc.contributor.authorMizutani, Tatsuaki-
dc.contributor.authorKano, Shin Ichi-
dc.contributor.authorHonda, Kenya-
dc.contributor.authorOhba, Yusuke-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorTaniguchi, Tadatsugu-
dc.date.accessioned2020-11-17T14:54:54Z-
dc.date.available2020-11-17T14:54:54Z-
dc.date.issued2005-
dc.identifier.citationNature, 2005, v. 434, n. 7030, p. 243-249-
dc.identifier.issn0028-0836-
dc.identifier.urihttp://hdl.handle.net/10722/291691-
dc.description.abstractThe activation of Toll-like receptors (TLRs) is central to innate and adaptive immunity1-3. All TLRs use the adaptor MyD88 for signalling4, but the mechanisms underlying the MyD88-mediated gene induction programme are as yet not fully under-stood. Here, we demonstrate that the transcription factor IRF-5 is generally involved downstream of the TLR-MyD88 signalling pathway for gene induction of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-12 and tumour-necrosis factor-α. In haematopoietic cells from mice deficient in the Irf5 gene (Irf5-/- mice), the induction of these cytokines by various TLR ligands is severely impaired, whereas interferon-α induction is normal. We also provide evidence that IRF-5 interacts with and is activated by MyD88 and TRAF6, and that TLR activation results in the nuclear translocation of IRF-5 to activate cytokine gene transcription. Consistently, Irf5-/- mice show resistance to lethal shock induced by either unmethylated DNA or lipopolysaccharide, which correlates with a marked decrease in the serum levels of proinflammatory cytokines. Thus, our study identifies IRF-5 as a new, principal downstream regulator of the TLR-MyD88 signalling pathway and a potential target of therapeutic intervention to control harmful immune responses.-
dc.languageeng-
dc.relation.ispartofNature-
dc.titleIntegral role of IRF-5 in the gene induction programme activated by Toll-like receptors-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/nature03308-
dc.identifier.pmid15665823-
dc.identifier.scopuseid_2-s2.0-15044345461-
dc.identifier.volume434-
dc.identifier.issue7030-
dc.identifier.spage243-
dc.identifier.epage249-
dc.identifier.isiWOS:000227494500052-
dc.identifier.f10001023866-
dc.identifier.issnl0028-0836-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats