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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-...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541364/ https://www.ncbi.nlm.nih.gov/pubmed/26286994 http://dx.doi.org/10.1038/srep13107 |
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author | Tserel, Liina Kolde, Raivo Limbach, Maia Tretyakov, Konstantin Kasela, Silva Kisand, Kai Saare, Mario Vilo, Jaak Metspalu, Andres Milani, Lili Peterson, Pärt |
author_facet | Tserel, Liina Kolde, Raivo Limbach, Maia Tretyakov, Konstantin Kasela, Silva Kisand, Kai Saare, Mario Vilo, Jaak Metspalu, Andres Milani, Lili Peterson, Pärt |
author_sort | Tserel, Liina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4541364 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45413642015-08-31 Age-related profiling of DNA methylation in CD8+ T cells reveals changes in immune response and transcriptional regulator genes Tserel, Liina Kolde, Raivo Limbach, Maia Tretyakov, Konstantin Kasela, Silva Kisand, Kai Saare, Mario Vilo, Jaak Metspalu, Andres Milani, Lili Peterson, Pärt Sci Rep Article 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. Nature Publishing Group 2015-08-19 /pmc/articles/PMC4541364/ /pubmed/26286994 http://dx.doi.org/10.1038/srep13107 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Tserel, Liina Kolde, Raivo Limbach, Maia Tretyakov, Konstantin Kasela, Silva Kisand, Kai Saare, Mario Vilo, Jaak Metspalu, Andres Milani, Lili Peterson, Pärt Age-related profiling of DNA methylation in CD8+ T cells reveals changes in immune response and transcriptional regulator genes |
title | Age-related profiling of DNA methylation in CD8+ T cells reveals changes in immune response and transcriptional regulator genes |
title_full | Age-related profiling of DNA methylation in CD8+ T cells reveals changes in immune response and transcriptional regulator genes |
title_fullStr | Age-related profiling of DNA methylation in CD8+ T cells reveals changes in immune response and transcriptional regulator genes |
title_full_unstemmed | Age-related profiling of DNA methylation in CD8+ T cells reveals changes in immune response and transcriptional regulator genes |
title_short | Age-related profiling of DNA methylation in CD8+ T cells reveals changes in immune response and transcriptional regulator genes |
title_sort | age-related profiling of dna methylation in cd8+ t cells reveals changes in immune response and transcriptional regulator genes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541364/ https://www.ncbi.nlm.nih.gov/pubmed/26286994 http://dx.doi.org/10.1038/srep13107 |
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