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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Essential role of TAK1 in thymocyte development and activation
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Essential role of TAK1 in thymocyte development and activation

机译:TAK1在胸腺细胞发育和激活中的重要作用

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摘要

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.
机译:TAK1蛋白激酶响应先天免疫途径中促炎性细胞因子和微生物病原体的刺激介导NF-κB的活化。但是,TAK1在适应性免疫途径中的生理功能尚不清楚。通过工程化T细胞中缺乏TAK1的小鼠,我们在这里显示TAK1对于胸腺细胞的发育和体内激活至关重要。 TAK1的缺失阻止了显示CD4或CD8的单阳性胸腺细胞的成熟,从而导致外周组织中T细胞的减少。缺乏TAK1的胸腺细胞无法激活NF-κB和JNK,并且在刺激时易于凋亡。我们的结果提供了遗传证据,证明TAK1是激活胸腺细胞中NF-κB所必需的,并暗示TAK1在先天和适应性免疫中都起着核心作用。

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