title: Interaction of Ets-1 with HDAC1 represses IL-10 expression in Th1 cells.
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.
authors.affiliation: School of Life Sciences and Immune Synapse Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, The Republic of Korea.
authors.forename: Choong-Gu
authors.initials: CG
authors.lastname: Lee
authors.forename: Ho-Keun
authors.initials: HK
authors.lastname: Kwon
authors.forename: Anupama
authors.initials: A
authors.lastname: Sahoo
authors.forename: Won
authors.initials: W
authors.lastname: Hwang
authors.forename: Jae-Seon
authors.initials: JS
authors.lastname: So
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Hwang
authors.forename: Chang-Suk
authors.initials: CS
authors.lastname: Chae
authors.forename: Gi-Cheon
authors.initials: GC
authors.lastname: Kim
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Hong-Seob
authors.initials: HS
authors.lastname: So
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Hwang
authors.forename: Roland
authors.initials: R
authors.lastname: Grenningloh
authors.forename: I-Cheng
authors.initials: IC
authors.lastname: Ho
authors.forename: Sin-Hyeog
authors.initials: SH
authors.lastname: Im
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050784:Proto-Oncogene Protein c-ets-1 / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: C494042:Ets1 protein, mouse; C556062:IL10 protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D016753:Interleukin-10; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1