期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 204, 期 5, 页码 1013-1024出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20061523
关键词
-
资金
- NIAID NIH HHS [P01 AI070167, AI070167] Funding Source: Medline
Interleukin-1 receptor-associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)- and T cell receptor (TCR)-mediated signaling leading to the activation of nuclear factor kappa B (NF-kappa B). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4(KN/KN) mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4(KN/KN) as well as IRAK-4(-/-) macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1-dependent and -independent pathways were involved in early induction of NF-kappa B-regulated genes in response to TLR ligands such as tumor necrosis factor alpha and I kappa B xi. In contrast to a previous paper (Suzuki, N., S. Suzuki, D. G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N. J. Chen, A. R. Elford, et al. 2006. Science. 311: 1927-1932), the TCR signaling was not impaired in IRAK-4(-/-) and IRAK-4(KN/KN) mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据