Age-related Profiling of DNA Methylation in CD8+ T Cells Reveals Changes in Immune Response and Transcriptional Regulator Genes

Overview

Journal Sci Rep

Specialty Science

Date 2015 Aug 20

PMID 26286994

Citations 93

Authors

Liina Tserel

Raivo Kolde

Maia Limbach

Konstantin Tretyakov

Silva Kasela

Kai Kisand

Mario Saare

Jaak Vilo

Andres Metspalu

Lili Milani

Part Peterson

Affiliations

Soon will be listed here.

Abstract

Human ageing affects the immune system resulting in an overall decline in immunocompetence. Although all immune cells are affected during aging, the functional capacity of T cells is most influenced and is linked to decreased responsiveness to infections and impaired differentiation. We studied age-related changes in DNA methylation and gene expression in CD4+ and CD8+ T cells from younger and older individuals. We observed marked difference between T cell subsets, with increased number of methylation changes and higher methylome variation in CD8+ T cells with age. The majority of age-related hypermethylated sites were located at CpG islands of silent genes and enriched for repressive histone marks. Specifically, in CD8+ T cell subset we identified strong inverse correlation between methylation and expression levels in genes associated with T cell mediated immune response (LGALS1, IFNG, CCL5, GZMH, CCR7, CD27 and CD248) and differentiation (SATB1, TCF7, BCL11B and RUNX3). Our results thus suggest the link between age-related epigenetic changes and impaired T cell function.

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