Age-related profiling of DNA methylation in CD8+ T cells reveals changes in immune response and transcriptional regulator genes.
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.
Molecular Pathology, Institute of Biomedical and Translational Medicine, University of Tartu, Tartu, Estonia.
Liina
L
Tserel
Institute of Computer Science, University of Tartu, Tartu, Estonia.
Raivo
R
Kolde
Molecular Pathology, Institute of Biomedical and Translational Medicine, University of Tartu, Tartu, Estonia.
Maia
M
Limbach
Institute of Computer Science, University of Tartu, Tartu, Estonia.
Konstantin
K
Tretyakov
1] Estonian Genome Center, University of Tartu, Tartu, Estonia [2] Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Silva
S
Kasela
Molecular Pathology, Institute of Biomedical and Translational Medicine, University of Tartu, Tartu, Estonia.
Kai
K
Kisand
Molecular Pathology, Institute of Biomedical and Translational Medicine, University of Tartu, Tartu, Estonia.
Mario
M
Saare
Institute of Computer Science, University of Tartu, Tartu, Estonia.
Jaak
J
Vilo
1] Estonian Genome Center, University of Tartu, Tartu, Estonia [2] Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Andres
A
Metspalu
Estonian Genome Center, University of Tartu, Tartu, Estonia.
Lili
L
Milani
Molecular Pathology, Institute of Biomedical and Translational Medicine, University of Tartu, Tartu, Estonia.
Pärt
P
Peterson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005786:Gene Expression Regulation; D042421:Histone Code / Q000235:genetics; D006801:Humans; D007109:Immunity / Q000235:genetics*; D008875:Middle Aged; D014158:Transcription, Genetic; D055815:Young Adult