Other
14 Authors
- Sen G,
- Xiao H,
- Kim TW,
- Qian W,
- Li X,
- Gilmour R,
- Hamilton T,
- Staschke K,
- Yao J,
- Min B,
- Oh KH,
- Bulek K,
- Vandenburg Y,
- Peters K
| First Author | Kim TW | Year | 2007 |
| Journal | J Exp Med | Volume | 204 |
| Issue | 5 | Pages | 1025-36 |
| PubMed ID | 17470642 | Mgi Jnum | J:125732 |
| Mgi Id | MGI:3759733 | Doi | 10.1084/jem.20061825 |
| Citation | Kim TW, et al. (2007) A critical role for IRAK4 kinase activity in Toll-like receptor-mediated innate immunity. J Exp Med 204(5):1025-36 |
| abstractText | 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. |
