Interaction of Ets-1 with HDAC1 Represses IL-10 Expression in Th1 Cells
Interaction of Ets-1 with HDAC1 Represses IL-10 Expression in Th1 Cells
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DOI：
10.4049/jimmunol.1101614
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发表时间：
2012-03-01
影响因子：
4.4
通讯作者：
Im, Sin-Hyeog
中科院分区：
文献类型：
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作者：
Lee, Choong-Gu;Kwon, Ho-Keun;Im, Sin-Hyeog
IL-10是一种多功能细胞因子，在免疫和耐受中起着至关重要的作用。IL-10由多种免疫细胞类型产生，包括B细胞和T细胞亚群。虽然Th 1细胞产生IL-10，但在常规刺激条件下，它们的表达水平远低于Th 2细胞。E26转化特异性1（Ets-1）转录因子作为IL-10基因在CD 4（+）T细胞中表达的负调节因子的潜在作用已经被提及。在这项研究中，我们研究了Ets-1介导的IL-10基因在Th 1细胞中的阻遏的潜在机制。与野生型Th 1细胞相比，Ets-1基因敲除的Th 1细胞表达IL-10的水平显著升高，与野生型Th 2细胞的水平相当。Ets-1敲除Th 1细胞中IL-10表达的上调伴随着染色质可及性的增强和组蛋白H3乙酰化在IL-10调控区的募集增加。反过来，Ets-1缺陷显着降低组蛋白去乙酰化酶1（HDAC 1）富集在IL 10调控区。HDAC家族抑制剂阿司他汀A治疗通过增加组蛋白H3乙酰化募集显著增加IL 10基因表达。我们进一步证明了Ets-1和HDAC 1之间的物理相互作用。Ets-1与HDAC 1的共表达协同抑制IL-10转录活性。总之，我们的数据表明，Ets-1与HDAC 1的相互作用抑制IL 10基因在Th 1细胞中的表达。免疫学杂志，2012，188：2244-2253。
IL-10 is a multifunctional cytokine that plays a crucial role in immunity and tolerance. IL-10 is produced by diverse immune cell types, including B cells and subsets of T cells. Although Th1 produce IL-10, their expression levels are much lower than Th2 cells under conventional stimulation conditions. The potential role of E26 transformation-specific 1 (Ets-1) transcription factor as a negative regulator for Il10 gene expression in CD4(+) T cells has been implicated previously. In this study, we investigated the underlying mechanism of Ets-1-mediated Il10 gene repression in Th1 cells. Compared with wild type Th1 cells, Ets-1 knockout Th1 cells expressed a significantly higher level of IL-10, which is comparable with that of wild type Th2 cells. Upregulation of IL-10 expression in Ets-1 knockout Th1 cells was accompanied by enhanced chromatin accessibility and increased recruitment of histone H3 acetylation at the Il10 regulatory regions. Reciprocally, Ets-1 deficiency significantly decreased histone deacetylase 1 (HDAC1) enrichment at the Il10 regulatory regions. Treatment with trichostatin A, an inhibitor of HDAC family, significantly increased Il10 gene expression by increasing histone H3 acetylation recruitment. We further demonstrated a physical interaction between Ets-1 and HDAC1. Coexpression of Ets-1 with HDAC1 synergistically repressed IL-10 transcription activity. In summary, our data suggest that an interaction of Ets-1 with HDAC1 represses the Il10 gene expression in Th1 cells. The Journal of Immunology, 2012, 188: 2244-2253.