IL-1R-Associated Kinase 4 Is Required for Lipopolysaccharide-Induced Activation of APC

Nobutaka Suzuki, Shinobu Suzuki, Urs Eriksson, Hiromitsu Hara, Christine Mirtosis, Nien Jung Chen, Teiji Wada, Denis Bouchard, Irene Hwang, Kiyoshi Takeda, Takashi Fujita, Sandy Der, Josef M. Penninger, Shizuo Akira, Takashi Saito, Wen Chen Yeh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


The bacterial product LPS is a critical stimulus for the host immune system in the response against the corresponding bacterial infection. LPS provides an activation stimulus for macrophages and a maturation signal for dendritic cells to set up innate and adaptive immune responses, respectively. The signaling cascade of myeloid differentiation factor 88>IL-1R-associated kinase (IRAK)>TNFR-associated factor 6 has been implicated in mediating LPS signaling. In this report, we studied the function of IRAK-4 in various LPS-induced signals. We found that IRAK-4-deficient cells were severely impaired in producing some IFN-regulated genes as well as inflammatory cytokines in response to LPS. Among the critical downstream signaling pathways induced by LPS, NF-κB activation but not IFN regulatory factor 3 or STAT1 activation was defective in cells lacking IRAK-4. IRAK-4 was also required for the proper maturation of dendritic cells by LPS stimulation, particularly in terms of cytokine production and the ability to stimulate Th cell differentiation. Our results demonstrate that IRAK-4 is critical for the LPS-induced activations of APCs.

Original languageEnglish
Pages (from-to)6065-6071
Number of pages7
JournalJournal of Immunology
Issue number11
StatePublished - 1 Dec 2003


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