Essential role of TAK1 in thymocyte development and activation
Essential role of TAK1 in thymocyte development and activation
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DOI：
10.1073/pnas.0603089103
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发表时间：
2006-08-01
影响因子：
11.1
通讯作者：
Chen, Zhijian J.
中科院分区：
文献类型：
--
作者：
Liu, Hong-Hsing;Xie, Min;Chen, Zhijian J.
在先天免疫途径中，蛋白激酶TAK1在促炎细胞因子和病原体的刺激下介导了核因子-kappaB的激活。然而，TAK1在获得性免疫途径中的生理功能尚不清楚。通过在T细胞中缺乏TAK1的工程小鼠，我们证明了TAK1对于体内胸腺细胞的发育和激活是必不可少的。TAK1的缺失阻止了表现为CD4或CD8的单一阳性胸腺细胞的成熟，导致周围组织中T细胞的减少。缺乏TAK1的胸腺细胞不能激活核因子-kappaB和JNK，在刺激下易发生凋亡。我们的结果提供了TAK1在胸腺细胞中激活核因子-kappaB所必需的遗传学证据，并提示TAK1在先天免疫和获得性免疫中发挥核心作用。
The protein kinase TAK1 mediates the activation of NF-kappa B in response to stimulation by proinflammatory cytokines and microbial pathogens in the innate immunity pathways. However, the physiological function of TAK1 in the adaptive immunity pathways is unclear. By engineering mice lacking TAK1 in T cells, here, we show that TAK1 is essential for thymocyte development and activation in vivo. Deletion of TAK1 prevented the maturation of single-positive thymocytes displaying CD4 or CD8, leading to reduction of T cells in the peripheral tissues. Thymocytes lacking TAK1 failed to activate NF-kappa B and JNK and were prone to apoptosis upon stimulation. Our results provide the genetic evidence that TAK1 is required for the activation of NF-kappa B in thymocytes and suggest that TAK1 plays a central role in both innate and adaptive immunity.