The role for DNA methylation in differentially regulating IL-7 receptor alpha expression by human T cells (94.22)

Abstract

Abstract IL-7 is critical for the development and survival of T cells. Recently, we found two subsets of human CD8+ T cells expressing IL-7Rahigh and IL-7Ralow with different cell survival responses to IL-7. Although these CD8+ T cell subsets have differential IL-7Ra gene expression, the mechanism for this is unknown. DNA methylation is an important gene regulatory mechanism and associated with inactivation of gene expression. Thus, we investigated the role for DNA methylation in differentially regulating IL-7Ra gene expression in human CD8+ T cells and Jurkat T cells. IL-7Rahigh CD8+ T cells had decreased methylation in the IL-7Ra gene promoter compared to IL-7Ralow CD8+ T cells and Jurkat T cells with low levels of IL-7Ra. Treating Jurkat T cells with 5-aza-2¡-deoxycytidine (5-aza-dC), which reduced DNA methylation, increased IL-7Ra expression. Plus, the unmethylated IL-7Ra gene promoter construct had higher levels of promoter activity than the methylated one as measured by a luciferase reporter assay. These findings suggest that a novel mechanism is involved in differentially regulating IL-7Ra expression in T cells through altering DNA methylation of the IL-7Ra gene promoter, and that methylation of this gene promoter could be a potential target for modifying IL-7-mediated T cell development and survival.