Identification of age-related changes in chromatin accessibility and gene expression in T cells from thymus to periphery

Abstract

Abstract Aging of immune system is characterized by progressive decline of physiological and cellular function of T cells, leading to a reduced immune function in the old. Recent studies of naïve T cells from young and old mice have identified age-related altered gene expressions, but the mechanisms underlying age associated changes of naïve T cells remain poorly understood. Here, we compared chromatin accessibility and the transcriptome in mature thymocytes and in naïve T cells of spleen between young (6–8 weeks) and old (95–114 weeks) C57BL/6 mice, using Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) and Agilent microarray methods, respectively. We identified age-related changes of chromatin accessibility that are correlated with the gene expression changes, providing a chromatin basis of age-related changes in gene expression. Interestingly, some age-related changes of CD4 and CD8 T cells in thymus did not retain in the spleen, and others appeared later only in the spleen, suggesting different tissue environment may contribute to the age-related changes of T cells. To directly address environmental effects, we currently examine changes of naïve T cells from old mouse before and after hosted in young mouse for 21 days in chromatin accessibility, transcriptomes, and protein expression. Collectively, these approaches will allow us to dissect the time and environmental influences in naïve T cell function in old mice. Our findings will have important implications both for better understanding the mechanisms underlying these age-related changes as well as opening potential new targets to mitigate the age-related reduced T cell functions.