Age-Associated Decline in Thymic B Cell Expression of Aire and Aire-Dependent Self-Antigens.
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.
['Cepeda|Sergio|S|', 'Cantu|Carolina|C|', 'Orozco|Stephanie|S|', 'Xiao|Yangming|Y|', 'Brown|Zoe|Z|', 'Semwal|Manpreet K|MK|', 'Venables|Thomas|T|', 'Anderson|Mark S|MS|', 'Griffith|Ann V|AV|']
D000328:Adult D000375:Aging D000818:Animals D001324:Autoantigens D001402:B-Lymphocytes D061167:Central Tolerance D002675:Child, Preschool D006801:Humans D007223:Infant D051379:Mice D008875:Middle Aged D013950:Thymus Gland D014157:Transcription Factors
B cell Aire aging thymus