Dynamic DNA methylation patterns across the mouse and human IL10 genes during CD4+ T cell activation; influence of IL-27

Christian M. Hedrich, Amritha Ramakrishnan, Djeneba Dabitao, Fengying Wang, Dilini Ranatunga, Jay Bream

Research output: Contribution to journalArticle

Abstract

IL-10 plays a critical role in controlling inflammation and the anti-inflammatory functions of IL-10 are regulated based on its coordinated expression from various cellular sources, most notably T cells. Although nearly all CD4+ subpopulations can express IL-10, surprisingly little is known about the molecular mechanisms which control IL-10 induction, particularly in humans. To examine the regulation of human IL-10 expression, we created the hIL10BAC transgenic mouse. As previously reported, we observed conservation of myeloid-derived IL-10 expression but found that human IL-10 was only weakly expressed in splenic CD4+ T cells from hIL10BAC mice. Since DNA methylation is an important determinant of gene expression profiles, we assessed the patterns of DNA methylation in the human and mouse IL10 genes in naïve and activated CD4+ T cells. Across mouse and human IL10 there were no obvious patterns of CpG methylation in naïve CD4+ T cells following polyclonal activation. Overall however, the human IL10 gene had significantly higher levels of DNA methylation. Interestingly, coculture with the IL-10-inducing cytokine IL-27 lead to a site-specific reduction in methylation of the mouse but not human IL10 gene. Demethylation was specifically localized to an intronic site adjacent to a known regulatory region. Our findings indicate that while the mouse and human IL10 genes undergo variable changes in DNA methylation during CD4+ T cell activation, IL-27 appears to influence DNA methylation in a particular intronic region thus associating with IL-10 expression.

Original languageEnglish (US)
Pages (from-to)73-81
Number of pages9
JournalMolecular Immunology
Volume48
Issue number1-3
DOIs
Publication statusPublished - Nov 2010

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Keywords

  • Cytokine
  • DNA methylation
  • Gene regulation
  • IL-10
  • IL-27
  • T cell

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

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