The chromatin accessibility signature of human immune aging stems from CD8+ T cells.
Duygu UcarEladio J MárquezCheng-Han ChungRadu MarchesRobert J RossiAsli UyarTe-Chia WuJoshy GeorgeMichael L StitzelA Karolina PaluckaGeorge A KuchelJacques F BanchereauPublished in: The Journal of experimental medicine (2017)
Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites. Combined analyses of chromatin accessibility and the transcriptome uncovered immune molecules activated/inactivated with aging and identified the silencing of the IL7R gene and the IL-7 signaling pathway genes as potential biomarkers. This signature is borne by memory CD8+ T cells, which exhibited an aging-related loss in binding of NF-κB and STAT factors. Thus, our study provides a unique and comprehensive approach to identifying candidate biomarkers and provides mechanistic insights into aging-associated immunodeficiency.
Keyphrases
- genome wide
- gene expression
- transcription factor
- dna damage
- signaling pathway
- immune response
- dna methylation
- single cell
- rna seq
- oxidative stress
- pi k akt
- copy number
- endothelial cells
- dendritic cells
- cell proliferation
- genome wide identification
- epithelial mesenchymal transition
- lps induced
- dna binding
- working memory
- toll like receptor
- kidney transplantation
- bioinformatics analysis