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

IL-10 plays a critical role in controlling inflammation and the anti-inflammatory functions of IL-10 Dare 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 MO genes in naive and activated CD4+ T cells Across mouse and human IL10 there were no obvious patterns of CpG methylation in naive 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 100 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 (C) 2010 Elsevier Ltd All rights reserved