Down-Regulation of IL-7Rα Expression in Human T Cells via DNA Methylation

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-7Rαhigh and IL-7Rαlow with different cell survival responses to IL-7. Although these CD8+ T cell subsets have differential IL-7Rα gene expression, the mechanism for this is unknown. DNA methylation is an important gene regulatory mechanism and is associated with the inactivation of gene expression. Thus, we investigated a role for DNA methylation in differentially regulating IL-7Rα gene expression in human CD8+ T cells and Jurkat T cells. IL-7RαhighCD8+ T cells had decreased methylation in the IL-7Rα gene promoter compared with IL-7RαlowCD8+ T cells and Jurkat T cells with low levels of IL-7Rα. Treating Jurkat T cells with 5-aza-2′-deoxycytidine, which reduced DNA methylation, increased IL-7Rα expression. Plus, the unmethylated IL-7Rα gene promoter construct had higher levels of promoter activity than the methylated one as measured by a luciferase reporter assay. These findings suggest that DNA methylation is involved in regulating IL-7Rα expression in T cells via affecting IL-7Rα gene promoter activity, and that the methylation of this gene promoter could be a potential target for modifying IL-7-mediated T cell development and survival.