We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A critical role for IRAK4 kinase activity in Toll-like receptor-mediated innate immunity.
- Authors
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
- Abstract
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 kappaB 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.
- Publication
The Journal of experimental medicine, 2007, Vol 204, Issue 5, p1025
- ISSN
0022-1007
- Publication type
Journal Article
- DOI
10.1084/jem.20061825