Interaction of Ets-1 with HDAC1 represses IL-10 expression in Th1 cells

CG Lee, HK Kwon, A Sahoo, W Hwang… - The Journal of …, 2012 - journals.aai.org
CG Lee, HK Kwon, A Sahoo, W Hwang, JS So, JS Hwang, CS Chae, GC Kim, JE Kim, HS So…
The Journal of Immunology, 2012journals.aai.org
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 …
Abstract
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.
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