Dynamic demethylation of the <i>IL2RA</i> promoter during <i>in vitro</i> CD4+ T cell activation in association with IL2RA expression

IL2RA, a subunit of the high affinity receptor for interleukin-2 (IL2), plays a crucial role in immune homeostasis. Notably, IL2RA expression is induced in CD4+ T cells in response to various stimuli and is constitutive in regulatory T cells (Tregs). We selected for our study 18 CpGs located within cognate regulatory regions of the <i>IL2RA</i> locus and characterized their methylation in naive, regulatory, and memory CD4+ T cells. We found that 5/18 CpGs (notably CpG + 3502) show dynamic, active demethylation during the <i>in vitro</i> activation of naive CD4+ T cells. Demethylation of these CpGs correlates with appearance of IL2RA protein at the cell surface. We found no influence of <i>cis</i> located SNP alleles upon CpG methylation. Treg cells show constitutive demethylation at all studied CpGs. Methylation of 9/18 CpGs, including CpG +3502, decreases with age. Our data thus identify CpG +3502 and a few other CpGs at the <i>IL2RA</i> locus as coordinated epigenetic regulators of IL2RA expression in CD4+ T cells. This may contribute to unravel how the <i>IL2RA</i> locus can be involved in immune physiology and pathology.