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

Choong Gu Lee, Ho Keun Kwon, Anupama Sahoo, Won Hwang, Jae Seon So, Ji Sun Hwang, Chang Suk Chae, Gi Cheon Kim, Jung Eun Kim, Hong Seob So, Eun Sook Hwang, Roland Grenningloh, I. Cheng Ho, Sin Hyeog Im

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish
Pages (from-to)2244-2253
Number of pages10
JournalJournal of Immunology
Volume188
Issue number5
DOIs
StatePublished - 1 Mar 2012

Fingerprint

Dive into the research topics of 'Interaction of Ets-1 with HDAC1 represses IL-10 expression in Th1 cells'. Together they form a unique fingerprint.

Cite this