Dynamic demethylation of the IL2RApromoter during in vitroCD4+ T cell activation in association with IL2RA expression

Autor: Belot, Marie-Pierre, Castell, Anne-Laure, Le Fur, Sophie, Bougnères, Pierre
Zdroj: Epigenetics; May 2018, Vol. 13 Issue: 5 p459-472, 14p
Abstrakt: ABSTRACTIL2RA, 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 IL2RAlocus 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 in vitroactivation of naive CD4+ T cells. Demethylation of these CpGs correlates with appearance of IL2RA protein at the cell surface. We found no influence of cislocated 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 IL2RAlocus as coordinated epigenetic regulators of IL2RA expression in CD4+ T cells. This may contribute to unravel how the IL2RAlocus can be involved in immune physiology and pathology.
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