Interleukin 2 gene transcription is regulated by Ikaros-induced changes in histone acetylation in anergic T cells
Interleukin 2 gene transcription is regulated by Ikaros-induced changes in histone acetylation in anergic T cells
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DOI：
10.1182/blood-2006-07-037754
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发表时间：
2007-04-01
期刊：
影响因子：
20.3
通讯作者：
Macian, Fernando
中科院分区：
文献类型：
--
作者：
Bandyopadhyay, Sanmay;Dure, Myrianne;Macian, Fernando
在T细胞中，无反应性可能是在缺乏共刺激的情况下由T细胞受体的不平衡刺激引起的。无反应性T细胞对新抗原受体接合无反应，并且不产生白细胞介素2。我们目前的证据表明，无能量刺激诱导组蛋白乙酰化，介导白细胞介素2表达的转录抑制的变化。响应于钙信号传导，无反应性T细胞上调lkaros的表达，lkaros是淋巴谱系确定所必需的锌指转录因子。Lkaros与白细胞介素2启动子结合，在那里它诱导组蛋白脱乙酰化。证实了lkaros在诱导T细胞无反应性中的作用，具有降低的lkaros活性的细胞显示出响应于无能量刺激的失活缺陷。我们提出了一个模型，在该模型中，耐受性刺激诱导白细胞介素2基因座上的表观遗传变化，该基因座负责稳定抑制这种细胞因子在无反应性T细胞中的表达。
In T cells anergy may be evoked by an unbalanced stimulation of the T-cell receptor in the absence of costimulation. Anergic T cells are unresponsive to new antigen receptor engagement and do not produce interleukin 2. We present evidence that anergizing stimuli induce changes in histone acetylation, which mediates transcriptional repression of interleukin 2 expression. In response to calcium signaling, anergic T cells up-regulate the expression of lkaros, a zinc finger transcription factor essential for lymphoid lineage determination. lkaros binds to the interleukin 2 promoter where it induces histone deacetylation. Confirming the role of lkaros in the induction of T-cell anergy, cells with reduced lkaros activity show defective inactivation in response to an anergizing stimulus. We propose a model in which tolerizing stimuli induce epigenetic changes on the interleukin 2 locus that are responsible for the stable inhibition of the expression of this cytokine in anergic T cells.