A critical role for the innate immune signaling molecule IRAK-4 in T cell activation
A critical role for the innate immune signaling molecule IRAK-4 in T cell activation
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DOI：
10.1126/science.1124256
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发表时间：
2006-03-31
期刊：
影响因子：
56.9
通讯作者：
Saito, T
中科院分区：
文献类型：
--
作者：
Suzuki, N;Suzuki, S;Saito, T
IRAK-4是一种蛋白激酶，在介导先天免疫应答信号中起关键作用。在这里，我们报道了IRAK-4信号对于引发适应性免疫反应也是必不可少的。因此，在缺乏IRAK-4的情况下，体内T细胞反应明显受损。在T细胞受体刺激下，IRAK-4被募集到T细胞脂筏中，在那里它诱导下游信号，包括通过与Zap70的关联激活蛋白激酶C θ。该信号通路被发现是核因子kappa b的最佳激活所必需的。我们的研究结果表明，T细胞使用这种先天免疫的关键调节剂来发展获得性免疫，这表明IRAK-4可能参与两个系统之间的直接信号串扰。
IRAK-4 is a protein kinase that is pivotal in mediating signals for innate immune responses. Here, we report that IRAK-4 signaling is also essential for eliciting adaptive immune responses. Thus, in the absence of IRAK-4, in vivo T cell responses were significantly impaired. Upon T cell receptor stimulation, IRAK-4 is recruited to T cell lipid rafts, where it induces downstream signals, including protein kinase C theta activation through the association with Zap70. This signaling pathway was found to be required for optimal activation of nuclear factor kappa B. Our findings suggest that T cells use this critical regulator of innate immunity for the development of acquired immunity, suggesting that IRAK-4 may be involved in direct signal cross talk between the two systems.