Rapid histone deacetylation and transient HDAC association in the IL-2 promoter region of TSST-1-stimulated T cells
Rapid histone deacetylation and transient HDAC association in the IL-2 promoter region of TSST-1-stimulated T cells
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DOI：
10.1016/j.imlet.2008.05.006
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发表时间：
2008-08-15
影响因子：
4.4
通讯作者：
Habu, Sonoko
中科院分区：
文献类型：
--
作者：
Kametani, Yoshie;Wang, Lili;Habu, Sonoko
目前尚不清楚超抗原如何诱导受刺激的T细胞无反应性。我们分析了白细胞介素-2（IL-2）启动子区的染色质状态的T细胞刺激中毒性休克综合征毒素-1（TSST-1）超抗原使用T细胞受体转基因T细胞卵清蛋白（OVA）和TSST-1。与OVA刺激相比，用TSST-1培养的初始T细胞在瞬时增强后显示较低的IL-2表达。巧合的是，在TSST-1刺激的T细胞中，IL-2启动子区域的乙酰化组蛋白H3（AcH 3）水平首先增强，然后降低。在AcH 3还原阶段，组蛋白脱乙酰基酶-1（HDAC 1）以TSST-1特异性方式与IL-2启动子区显着相关，但没有HDAC 1过表达。用HDAC抑制剂预处理可阻止HDAC 1结合和IL-2抑制的增强，但一旦无反应性状态就不能。这些结果表明，HDAC 1在IL-2启动子区的早期募集已经建立。TSST-1刺激阶段在sAg诱导的无反应性中起关键作用。(C)2008 Elsevier B. V.保留所有权利。
It remains unclear how superantigen induces unresponsiveness in stimulated T cells. We analyzed the chromatin status of the interleukin-2 (IL-2) promoter region in T cells stimulated with toxic shock syndrome toxin-1 (TSST-1) superantigen using T cell receptor-transgenic T cells responding to ovalbumin (OVA) and TSST-1. Compared to OVA stimulation, naive T cells cultured with TSST-1 showed lower IL-2 expression after transient enhancement. Coincidentally, the acetylated histone H3 (AcH3) level at the IL-2 promoter region was first enhanced, and then decreased, in TSST-1-stimulated T cells. At the reduction stage of AcH3, histone deacetylase-1 (HDAC1) was markedly associated with the IL-2 promoter region in a TSST-1-specific manner without HDAC1 over-expression. The enhancement of HDAC1 association and IL-2 suppression was prevented by pre-treatment with HDAC inhibitor, but not once the anergy status These results suggest that recruitment of HDAC1 in the IL-2 promoter region at the early was established. stimulation stage with TSST-1 plays a pivotal role in sAg-induced anergy. (C) 2008 Elsevier B.V. All rights reserved.