Intestinal T cell homeostasis disrupted by epigenetic alterations
A precise balance between mature T cell subsets is important for intestinal homeostasis.
Disruption of T cell populations underlies autoimmune colitis, including inflammatory bowel disease (IBD). Specific transcriptional programs are activated to determine the differentiation fate of naïve T cells; however, the role of epigenetic regulation in T cell maturation in the intestine is unclear.
In this issue of the Journal of Clinical Investigation, Colby Zaph and colleagues from the University of British Columbia used a murine T cell transfer model, to demonstrate that T cell-specific expression of the histone lysine methyltransferase G9A is required for pathogenic T cell responses and colitis progression.
G9A expression in naïve T cells prevented development of Th17 and Treg subsets and was associated with increased histone methylation. Pharmacologic inhibition of G9A restored the ability of T cells to differentiate into Treg and Th17 subsets, suggesting that targeting G9A may relieve intestinal inflammatory disease.