IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508.
IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508.
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DOI：
10.1084/jem.20051044
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发表时间：
2005-11-07
期刊：
影响因子：
--
通讯作者：
Glimcher LH
中科院分区：
文献类型：
--
作者：
Hwang ES;Hong JH;Glimcher LH
白细胞介素（IL）-2是由初始Th细胞在初级应答中产生的主要细胞因子。它是Th前体细胞增殖和分化为效应细胞所必需的。最初的高水平IL-2的生产，其次是其下降，并伴随诱导的细胞因子是典型的分化状态。虽然负责IL-2的早期诱导的因素是明确的，负责其在Th发育的后期阶段下调的机制还没有被研究。我们实验室的前期工作揭示了T盒转录因子T-bet在IL-2基因转录中的阻遏功能。在这里，我们报告说，T-betS 508所需的最佳抑制IL-2的生产在发展中的Th 1细胞。酪蛋白激酶I和糖原合成酶激酶-3激酶对T-betS 508的磷酸化伴随T-bet与RelA核因子-κB转录因子的相互作用。T-bet和RelA的异源二聚化干扰RelA与IL-2启动子的结合，并因此干扰RelA对IL-2基因的转录激活。
Interleukin (IL)-2 is the predominant cytokine that is produced by naive Th cells in a primary response. It is required for proliferation and differentiation of Th precursor cells into effector cells. Initial high-level IL-2 production is followed by its decline, and the concomitant induction of cytokines that are typical of the differentiated state. Although the factors that are responsible for the early induction of IL-2 are well defined, the mechanisms that are responsible for its down-regulation in later stages of Th development have not been studied as much. Previous work from our laboratory revealed a repressor function for the T-box transcription factor, T-bet, in IL-2 gene transcription. Here, we report that T-betS508 is required for the optimal repression of IL-2 production in developing Th1 cells. Phosphorylation of T-betS508 by casein kinase I and glycogen synthase kinase-3 kinases accompanies T-bet's interaction with the RelA nuclear factor–κB transcription factor. Heterodimerization of T-bet and RelA interferes with the binding of RelA to the IL-2 promoter, and hence, transcriptional activation of the IL-2 gene by RelA.
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