The chromatin accessibility signature of human immune aging stems from CD8(+) T cells.
Document Type
Article
Publication Date
10-2-2017
JAX Source
J Exp Med 2017 Oct 2; 214(10):3123-3144
Volume
214
Issue
10
First Page
3123
Last Page
3144
ISSN
1540-9538
PMID
28904110
DOI
https://doi.org/10.1084/jem.20170416
Abstract
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. J Exp Med 2017 Oct 2; 214(10):3123-3144.
Recommended Citation
Ucar D,
Marquez E,
Chung C,
Marches R,
Rossi R,
Uyar A,
Wu T,
George J,
Stitzel ML,
Palucka A,
Kuchel G,
Banchereau J.
The chromatin accessibility signature of human immune aging stems from CD8(+) T cells. J Exp Med 2017 Oct 2; 214(10):3123-3144