DNA Methylation Regulates the Differential Expression of CX3CR1 on Human IL-7R?low and IL-7R?high Effector Memory CD8+ T Cells with Distinct Migratory Capacities to the Fractalkine.

ABSTRACT: DNA methylation is an epigenetic mechanism that modulates gene expression in mammalian cells including T cells. Memory T cells are heterogeneous populations. Human effector memory (EM) CD8(+) T cells in peripheral blood contain two cell subsets with distinct traits that express low and high levels of the IL-7R?. However, epigenetic mechanisms involved in defining such cellular traits are largely unknown. In this study, we use genome-wide DNA methylation and individual gene expression to show the possible role of DNA methylation in conferring distinct traits of chemotaxis and inflammatory responses in human IL-7R?(low) and IL-7R?(high) EM CD8(+) T cells. In particular, IL-7R?(low) EM CD8(+) T cells had increased expression of CX3CR1 along with decreased DNA methylation in the CX3CR1 gene promoter compared with IL-7R?(high) EM CD8(+) T cells. Altering the DNA methylation status of the CX3CR1 gene promoter changed its activity and gene expression. IL-7R?(low) EM CD8(+) T cells had an increased migratory capacity to the CX3CR1 ligand fractalkine compared with IL-7R?(high) EM CD8(+) T cells, suggesting an important biological outcome of the differential expression of CX3CR1. Moreover, IL-7R?(low) EM CD8(+) T cells induced fractalkine expression on endothelial cells by producing IFN-? and TNF-?, forming an autocrine amplification loop. Overall, our study shows the role of DNA methylation in generating unique cellular traits in human IL-7R?(low) and IL-7R?(high) EM CD8(+) T cells, including differential expression of CX3CR1, as well as potential biological implications of this differential expression.

SUBMITTER: Shin MS 

PROVIDER: S-EPMC4561204 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature