Cargando…
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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782141061781520384 |
---|---|
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. |
format | Text |
id | pubmed-2118590 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kimtaewhan acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT staschkekirk acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT bulekkatarzyna acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT yaojianhong acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT peterskristi acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT ohkeunhee acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT vandenburgyvonne acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT xiaohui acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT qianwen acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT hamiltontom acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT minbooki acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT senganes acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT gilmourraymond acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT lixiaoxia acriticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT kimtaewhan criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT staschkekirk criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT bulekkatarzyna criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT yaojianhong criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT peterskristi criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT ohkeunhee criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT vandenburgyvonne criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT xiaohui criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT qianwen criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT hamiltontom criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT minbooki criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT senganes criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT gilmourraymond criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity AT lixiaoxia criticalroleforirak4kinaseactivityintolllikereceptormediatedinnateimmunity |