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A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity

IRAK4 is a member of IL-1 receptor (IL-1R)–associated kinase (IRAK) family and has been shown to play an essential role in Toll-like receptor (TLR)–mediated signaling. We recently generated IRAK4 kinase-inactive knock-in mice to examine the role of kinase activity of IRAK4 in TLR-mediated signaling...

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Autores principales: Kim, Tae Whan, Staschke, Kirk, Bulek, Katarzyna, Yao, Jianhong, Peters, Kristi, Oh, Keun-Hee, Vandenburg, Yvonne, Xiao, Hui, Qian, Wen, Hamilton, Tom, Min, Booki, Sen, Ganes, Gilmour, Raymond, Li, Xiaoxia
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118590/
https://www.ncbi.nlm.nih.gov/pubmed/17470642
http://dx.doi.org/10.1084/jem.20061825
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author Kim, Tae Whan
Staschke, Kirk
Bulek, Katarzyna
Yao, Jianhong
Peters, Kristi
Oh, Keun-Hee
Vandenburg, Yvonne
Xiao, Hui
Qian, Wen
Hamilton, Tom
Min, Booki
Sen, Ganes
Gilmour, Raymond
Li, Xiaoxia
author_facet Kim, Tae Whan
Staschke, Kirk
Bulek, Katarzyna
Yao, Jianhong
Peters, Kristi
Oh, Keun-Hee
Vandenburg, Yvonne
Xiao, Hui
Qian, Wen
Hamilton, Tom
Min, Booki
Sen, Ganes
Gilmour, Raymond
Li, Xiaoxia
author_sort Kim, Tae Whan
collection PubMed
description IRAK4 is a member of IL-1 receptor (IL-1R)–associated kinase (IRAK) family and has been shown to play an essential role in Toll-like receptor (TLR)–mediated signaling. We recently generated IRAK4 kinase-inactive knock-in mice to examine the role of kinase activity of IRAK4 in TLR-mediated signaling pathways. The IRAK4 kinase–inactive knock-in mice were completely resistant to lipopolysaccharide (LPS)- and CpG-induced shock, due to impaired TLR-mediated induction of proinflammatory cytokines and chemokines. Although inactivation of IRAK4 kinase activity did not affect the levels of TLR/IL-1R–mediated nuclear factor κB activation, a reduction of LPS-, R848-, and IL-1–mediated mRNA stability contributed to the reduced cytokine and chemokine production in bone marrow–derived macrophages from IRAK4 kinase–inactive knock-in mice. Both TLR7- and TLR9-mediated type I interferon production was abolished in plasmacytoid dendritic cells isolated from IRAK4 knock-in mice. In addition, influenza virus–induced production of interferons in plasmacytoid DCs was also dependent on IRAK4 kinase activity. Collectively, our results indicate that IRAK4 kinase activity plays a critical role in TLR-dependent immune responses.
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spelling pubmed-21185902007-12-13 A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity Kim, Tae Whan Staschke, Kirk Bulek, Katarzyna Yao, Jianhong Peters, Kristi Oh, Keun-Hee Vandenburg, Yvonne Xiao, Hui Qian, Wen Hamilton, Tom Min, Booki Sen, Ganes Gilmour, Raymond Li, Xiaoxia J Exp Med Articles IRAK4 is a member of IL-1 receptor (IL-1R)–associated kinase (IRAK) family and has been shown to play an essential role in Toll-like receptor (TLR)–mediated signaling. We recently generated IRAK4 kinase-inactive knock-in mice to examine the role of kinase activity of IRAK4 in TLR-mediated signaling pathways. The IRAK4 kinase–inactive knock-in mice were completely resistant to lipopolysaccharide (LPS)- and CpG-induced shock, due to impaired TLR-mediated induction of proinflammatory cytokines and chemokines. Although inactivation of IRAK4 kinase activity did not affect the levels of TLR/IL-1R–mediated nuclear factor κB activation, a reduction of LPS-, R848-, and IL-1–mediated mRNA stability contributed to the reduced cytokine and chemokine production in bone marrow–derived macrophages from IRAK4 kinase–inactive knock-in mice. Both TLR7- and TLR9-mediated type I interferon production was abolished in plasmacytoid dendritic cells isolated from IRAK4 knock-in mice. In addition, influenza virus–induced production of interferons in plasmacytoid DCs was also dependent on IRAK4 kinase activity. Collectively, our results indicate that IRAK4 kinase activity plays a critical role in TLR-dependent immune responses. The Rockefeller University Press 2007-05-14 /pmc/articles/PMC2118590/ /pubmed/17470642 http://dx.doi.org/10.1084/jem.20061825 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Kim, Tae Whan
Staschke, Kirk
Bulek, Katarzyna
Yao, Jianhong
Peters, Kristi
Oh, Keun-Hee
Vandenburg, Yvonne
Xiao, Hui
Qian, Wen
Hamilton, Tom
Min, Booki
Sen, Ganes
Gilmour, Raymond
Li, Xiaoxia
A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity
title A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity
title_full A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity
title_fullStr A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity
title_full_unstemmed A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity
title_short A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity
title_sort critical role for irak4 kinase activity in toll-like receptor–mediated innate immunity
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118590/
https://www.ncbi.nlm.nih.gov/pubmed/17470642
http://dx.doi.org/10.1084/jem.20061825
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