TAK1在胸腺细胞发育和激活中的重要作用。
Essential role of TAK1 in thymocyte development and activation.
作者信息
Liu Hong-Hsing, Xie Min, Schneider Michael D, Chen Zhijian J
机构信息
Department of Molecular Biology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
出版信息
Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11677-82. doi: 10.1073/pnas.0603089103. Epub 2006 Jul 20.
Abstract
The protein kinase TAK1 mediates the activation of NF-kappaB 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-kappaB and JNK and were prone to apoptosis upon stimulation. Our results provide the genetic evidence that TAK1 is required for the activation of NF-kappaB in thymocytes and suggest that TAK1 plays a central role in both innate and adaptive immunity.
摘要
蛋白激酶TAK1在天然免疫途径中响应促炎细胞因子和微生物病原体的刺激介导核因子-κB（NF-κB）的激活。然而，TAK1在适应性免疫途径中的生理功能尚不清楚。通过构建T细胞中缺乏TAK1的小鼠，我们在此表明TAK1对于体内胸腺细胞的发育和激活至关重要。TAK1的缺失阻止了表达CD4或CD8的单阳性胸腺细胞的成熟，导致外周组织中T细胞减少。缺乏TAK1的胸腺细胞在受到刺激时无法激活NF-κB和JNK，并且易于凋亡。我们的结果提供了基因证据，表明TAK1是胸腺细胞中NF-κB激活所必需的，并表明TAK1在天然免疫和适应性免疫中均发挥核心作用。
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