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Locus-Specific Reversible DNA Methylation Regulates Transient IL-10 Expression in Th1 Cells

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Title
Locus-Specific Reversible DNA Methylation Regulates Transient IL-10 Expression in Th1 Cells
Author(s)
Won Hwang; Choong-Gu Lee; Changhon Lee; Ravi Verma; Dipayan Rudra; Park ZY; Sin Hyeog Im
Publication Date
2018-03
Journal
JOURNAL OF IMMUNOLOGY, v.200, no.5, pp.1865 - 1875
Publisher
AMER ASSOC IMMUNOLOGISTS
Abstract
IL-10 is a pleiotropic cytokine with multifaceted functions in establishing immune homeostasis. Although expressed by Th1 and Th2 cells, conventional Th1 cells produce marginal levels of IL-10 compared with their Th2 counterparts. In this study, we investigated the epigenetic mechanisms of Il-10 gene expression in Th1 cells. Bioinformatics EMBOSS CpG plot analysis and bisulfite pyrosequencing revealed three CpG DNA methylation sites in the Il-10 gene locus. Progressive DNA methylation at all of the CpG regions of interest (ROIs) established a repressive program of Il-10 gene expression in Th1 cells. Interestingly, Th1 cells treated with IL-12 and IL-27 cytokines, thereby mimicking a chronic inflammatory condition in vivo, displayed a significant increase in IL-10 production that was accompanied by selective DNA demethylation at ROI 3 located in intron 3. IL-10–producing T cells isolated from lymphocytic choriomeningitis virus–infected mice also showed enhanced DNA demethylation at ROI 3. Binding of STAT1 and STAT3 to demethylated ROI 3 enhanced IL-10 expression in an IL-12/IL-27–dependent manner. Accordingly, CD4+ T cells isolated from STAT1- or STAT3-knockout mice were significantly defective in IL-10 production. Our data suggest that, although stably maintained DNA methylation at the promoter may repress IL-10 expression in Th1 cells, locusspecific reversible DNA demethylation may serve as a threshold platform to control transient Il-10 gene expression. Copyright 2018 by The American Association of Immunologists, Inc.
URI
https://pr.ibs.re.kr/handle/8788114/4375
ISSN
0022-1767
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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(2018_W_Hwang)Locus-Specific Reversible DNA Methylation Regulates Transient IL-10 Expression in Th1 Cells.pdfDownload

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