Dec2 Promotes Th2 Cell Differentiation by Enhancing IL-2R Signaling

Dec2 Promotes Th2 Cell Differentiation by Enhancing IL-2R Signaling
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Dec2 通过增强 IL-2R 信号传导促进 Th2 细胞分化

DOI:
10.4049/jimmunol.0900975
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发表时间:
2009-11-15
影响因子:
4.4
通讯作者:
Sun, Bing
Sun, Bing
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Zhiduo;Li, Zhenhu;Sun, Bing

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Th细胞的分化在不同阶段受到数千个基因的精确调控。在本研究中,我们证明Dec2是属于bHLH(碱性螺旋-环-螺旋)超家族的转录因子,在Th2分化过程中被逐渐诱导,特别是在晚期。逆转录病毒介导的基因转移或转基因操作证明,上调的 Dec2 在 Th2 诱导条件下可以强烈促进 Th2 发育。此外,在 Dec2 转基因小鼠体内也可检测到 Th2 反应的增强。相反,RNA 干扰介导的内源性 Dec2 抑制可能会减弱 Th2 分化。最后,我们表明,Th2 发育增强至少部分是由于 Dec2 引起的 CD25 表达大幅上调,从而导致对 IL-2 刺激的高反应性。免疫学杂志,2009,183:6320-6329。
Th cell differentiation is precisely regulated by thousands of genes at different stages. In the present study, we demonstrate that Dec2, a transcription factor belonging to the bHLH (basic helix-loop-helix) superfamily, is progressively induced during the course of Th2 differentiation, especially at the late stage. The up-regulated Dec2 can strongly promote Th2 development under Th2-inducing conditions, as evidenced by retrovirus-mediated gene transfer or transgenic manipulation. In addition, an enhancement of Th2 responses is also detectable in Dec2 transgenic mice in vivo. Conversely, RNA interference-mediated suppression of endogenous Dec2 could attenuate Th2 differentiation. Finally, we show that the enhanced Th2 development is at least in part due to substantial up-regulation of CD25 expression elicited by Dec2, thereby resulting in hyperresponsiveness to IL-2 stimulation. The Journal of Immunology, 2009, 183: 6320-6329.