IL-1 Receptor-Associated Kinase 4 Is Essential for IL-18-Mediated NK and Th1 Cell Responses

Content Provider	Scilit
Author	Suzuki, Nobutaka Chen, Nien-Jung Millar, Douglas G. Suzuki, Shinobu Horacek, Thomas Hara, Hiromitsu Bouchard, Denis Nakanishi, Kenji Penninger, Josef M. Ohashi, Pamela S. Yeh, Wen-Chen
Copyright Year	2003
Description	IL-18 is an important cytokine for both innate and adaptive immunity. NK T cells and Th1 cells depend on IL-18 for their divergent functions. The IL-18R, IL-1R, and mammalian Toll-like receptors (TLRs) share homologous intracellular domains known as the TLR/IL-1R/plant R domain. Previously, we reported that IL-1R-associated kinase (IRAK)-4 plays a critical role in IL-1R and TLR signaling cascades and is essential for the innate immune response. Because TLR/IL-1R/plant R-containing receptors mediate signal transduction in a similar fashion, we investigated the role of IRAK-4 in IL-18R signaling. In this study, we show that IL-18-induced responses such as NK cell activity, Th1 IFN-γ production, and Th1 cell proliferation are severely impaired in IRAK-4-deficient mice. $IRAK-4^{−/−}$ Th1 cells also do not exhibit NF-κB activation or IκB degradation in response to IL-18. Moreover, AP-1 activation which is triggered by c-Jun N-terminal kinase activation is also completely inhibited in $IRAK-4^{−/−}$ Th1 cells. These results suggest that IRAK-4 is an essential component of the IL-18 signaling cascade.
Ending Page	4035
Page Count	5
Starting Page	4031
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.170.8.4031
Alternate Webpage(s)	http://www.jimmunol.org/content/170/8/4031.full.pdf
Journal	The Journal of Immunology
Issue Number	8
Volume Number	170
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2003-04-15
Access Restriction	Open
Subject Keyword	Innate Immune Th1 Cells 1r/plant Tlr/il
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology