Age-Associated Decline in Thymic B Cell Expression of Aire and Aire-Dependent Self-Antigens

Sergio Cepeda, Carolina Cantu, Stephanie Orozco, Yangming Xiao, Zoe Brown, Manpreet K. Semwal, Thomas Venables, Mark S. Anderson, Ann V Griffith

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Although autoimmune disorders are a significant source of morbidity and mortality in older individuals, the mechanisms governing age-associated increases in susceptibility remain incompletely understood. Central T cell tolerance is mediated through presentation of self-antigens by cells constituting the thymic microenvironment, including epithelial cells, dendritic cells, and B cells. Medullary thymic epithelial cells (mTECs) and B cells express distinct cohorts of self-antigens, including tissue-restricted self-antigens (TRAs), such that developing T cells are tolerized to antigens from peripheral tissues. We find that expression of the TRA transcriptional regulator Aire, as well as Aire-dependent genes, declines with age in thymic B cells in mice and humans and that cell-intrinsic and cell-extrinsic mechanisms contribute to the diminished capacity of peripheral B cells to express Aire within the thymus. Our findings indicate that aging may diminish the ability of thymic B cells to tolerize T cells, revealing a potential mechanistic link between aging and autoimmunity. Mechanisms governing age-associated increases in autoimmunity remain elusive. Expression of Aire and downstream self-antigens by thymic B cells helps tolerize developing T cells. Cepeda et al. report age-associated declines in expression of Aire and self-antigen genes in thymic B cells concomitant with increases in T-bet and IgG2a expression.

Original languageEnglish (US)
Pages (from-to)1276-1287
Number of pages12
JournalCell Reports
Volume22
Issue number5
DOIs
StatePublished - Jan 30 2018

Keywords

  • aging
  • Aire
  • B cell
  • thymus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Cepeda, S., Cantu, C., Orozco, S., Xiao, Y., Brown, Z., Semwal, M. K., Venables, T., Anderson, M. S., & Griffith, A. V. (2018). Age-Associated Decline in Thymic B Cell Expression of Aire and Aire-Dependent Self-Antigens. Cell Reports, 22(5), 1276-1287. https://doi.org/10.1016/j.celrep.2018.01.015