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- Publisher Website: 10.1038/nature736
- Scopus: eid_2-s2.0-0037129212
- PMID: 11923871
- WOS: WOS:000175033500045
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Article: Severe impairment of interleukin-1 and toll-like receptor signalling in mice lacking IRAK-4
Title | Severe impairment of interleukin-1 and toll-like receptor signalling in mice lacking IRAK-4 |
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Authors | |
Issue Date | 2002 |
Citation | Nature, 2002, v. 416, n. 6882, p. 750-754 How to Cite? |
Abstract | Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns, and members of the pro-inflammatory interleukin-1 receptor (IL-1R) family, share homologies in their cytoplasmic domains called Toll/IL-IR/plant R gene homology (TIR) domains. Intracellular signalling mechanisms mediated by TIRs are similar, with MyD88 (refs 5-8) and TRAF6 (refs 9, 10) having critical roles. Signal transduction between MyD88 and TRAF6 is known to involve the serine-threonine kinase IL-1 receptor-associated kinase 1 (IRAK-1) and two homologous proteins, IRAK-2 (ref. 12) and IRAK-M. However, the physiological functions of the IRAK molecules remain unclear, and gene-targeting studies have shown that IRAK-1 is only partially required for IL-1R and TLR signalling. Here we show by genetargeting that IRAK-4, an IRAK molecule closely related to the Drosophila Pelle protein, is indispensable for the responses of animals and cultured cells to IL-1 and ligands that stimulate various TLRs. IRAK-4-deficient animals are completely resistant to a lethal dose of lipopolysaccharide (LPS). In addition, animals lacking IRAK-4 are severely impaired in their responses to viral and bacterial challenges. Our results indicate that IRAK-4 has an essential role in innate immunity. |
Persistent Identifier | http://hdl.handle.net/10722/291618 |
ISSN | 2023 Impact Factor: 50.5 2023 SCImago Journal Rankings: 18.509 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Suzuki, Nobutaka | - |
dc.contributor.author | Suzuki, Shinobu | - |
dc.contributor.author | Duncan, Gordon S. | - |
dc.contributor.author | Millar, Douglas G. | - |
dc.contributor.author | Wada, Teiji | - |
dc.contributor.author | Mirtsos, Christine | - |
dc.contributor.author | Takada, Hidetoshi | - |
dc.contributor.author | Wakeham, Andrew | - |
dc.contributor.author | Itie, Annick | - |
dc.contributor.author | Li, Shyun | - |
dc.contributor.author | Penninger, Josef M. | - |
dc.contributor.author | Wesche, Holger | - |
dc.contributor.author | Ohashi, Pamela S. | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Yeh, Wen Chen | - |
dc.date.accessioned | 2020-11-17T14:54:45Z | - |
dc.date.available | 2020-11-17T14:54:45Z | - |
dc.date.issued | 2002 | - |
dc.identifier.citation | Nature, 2002, v. 416, n. 6882, p. 750-754 | - |
dc.identifier.issn | 0028-0836 | - |
dc.identifier.uri | http://hdl.handle.net/10722/291618 | - |
dc.description.abstract | Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns, and members of the pro-inflammatory interleukin-1 receptor (IL-1R) family, share homologies in their cytoplasmic domains called Toll/IL-IR/plant R gene homology (TIR) domains. Intracellular signalling mechanisms mediated by TIRs are similar, with MyD88 (refs 5-8) and TRAF6 (refs 9, 10) having critical roles. Signal transduction between MyD88 and TRAF6 is known to involve the serine-threonine kinase IL-1 receptor-associated kinase 1 (IRAK-1) and two homologous proteins, IRAK-2 (ref. 12) and IRAK-M. However, the physiological functions of the IRAK molecules remain unclear, and gene-targeting studies have shown that IRAK-1 is only partially required for IL-1R and TLR signalling. Here we show by genetargeting that IRAK-4, an IRAK molecule closely related to the Drosophila Pelle protein, is indispensable for the responses of animals and cultured cells to IL-1 and ligands that stimulate various TLRs. IRAK-4-deficient animals are completely resistant to a lethal dose of lipopolysaccharide (LPS). In addition, animals lacking IRAK-4 are severely impaired in their responses to viral and bacterial challenges. Our results indicate that IRAK-4 has an essential role in innate immunity. | - |
dc.language | eng | - |
dc.relation.ispartof | Nature | - |
dc.title | Severe impairment of interleukin-1 and toll-like receptor signalling in mice lacking IRAK-4 | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1038/nature736 | - |
dc.identifier.pmid | 11923871 | - |
dc.identifier.scopus | eid_2-s2.0-0037129212 | - |
dc.identifier.volume | 416 | - |
dc.identifier.issue | 6882 | - |
dc.identifier.spage | 750 | - |
dc.identifier.epage | 754 | - |
dc.identifier.isi | WOS:000175033500045 | - |
dc.identifier.f1000 | 1005426 | - |
dc.identifier.issnl | 0028-0836 | - |