Frontiers in Cell and Developmental Biology (Feb 2021)

Age-Related Gene Alteration in Naïve and Memory T cells Using Precise Age-Tracking Model

  • Xiaofeng Yang,
  • Xiaofeng Yang,
  • Xiaofeng Yang,
  • Xin Wang,
  • Xin Wang,
  • Xin Wang,
  • Lei Lei,
  • Lei Lei,
  • Lei Lei,
  • Lina Sun,
  • Lina Sun,
  • Anjun Jiao,
  • Anjun Jiao,
  • Anjun Jiao,
  • Kun Zhu,
  • Kun Zhu,
  • Tao Xie,
  • Tao Xie,
  • Haiyan Liu,
  • Haiyan Liu,
  • Xingzhe Zhang,
  • Xingzhe Zhang,
  • Yanhong Su,
  • Yanhong Su,
  • Cangang Zhang,
  • Cangang Zhang,
  • Lin Shi,
  • Lin Shi,
  • Dan Zhang,
  • Dan Zhang,
  • Huiqiang Zheng,
  • Huiqiang Zheng,
  • Jiahui Zhang,
  • Jiahui Zhang,
  • Xiaobin Liu,
  • Xiaobin Liu,
  • Xin Wang,
  • Xin Wang,
  • Xiaobo Zhou,
  • Xiaobo Zhou,
  • Chenming Sun,
  • Chenming Sun,
  • Baojun Zhang,
  • Baojun Zhang,
  • Baojun Zhang

DOI
https://doi.org/10.3389/fcell.2020.624380
Journal volume & issue
Vol. 8

Abstract

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In aged individuals, age-related changes in immune cells, especially T cell deficiency, are associated with an increased incidence of infection, tumor, and autoimmune disease, as well as an impaired response to vaccination. However, the features of gene expression levels in aged T cells are still unknown. Our previous study successfully tracked aged T cells generated from one wave of developing thymocytes of young age by a lineage-specific and inducible Cre-controlled reporter (TCRδCreERR26ZsGreen mouse strain). In this study, we utilized this model and genome-wide transcriptomic analysis to examine changes in gene expression in aged naïve and memory T cell populations during the aging process. We identified profound gene alterations in aged CD4 and CD8 T cells. Both aged CD4+ and CD8+ naïve T cells showed significantly decreased organelle function. Importantly, genes associated with lymphocyte activation and function demonstrated a significant increase in aged memory T cells, accompanied by upregulation of immunosuppressive markers and immune checkpoints, revealing an abnormal T cell function in aged cells. Furthermore, aging significantly affects T cell survival and death signaling. While aged CD4 memory T cells exhibited pro-apoptotic gene signatures, aged CD8 memory T cells expressed anti-apoptotic genes. Thus, the transcriptional analysis of gene expression and signaling pathways in aged T cell subsets shed light on our understanding of altered immune function with aging, which will have great potential for clinical interventions for older adults.

Keywords