Article ; Online: Age-Associated Decline in Thymic B Cell Expression of Aire and Aire-Dependent Self-Antigens
Cell Reports, Vol 22, Iss 5, Pp 1276-
2018 Volume 1287
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 ... ...
| 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. |
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| Keywords | thymus ; B cell ; aging ; Aire ; Biology (General) ; QH301-705.5 |
| Subject code | 612 |
| Language | English |
| Publishing date | 2018-01-01T00:00:00Z |
| Publisher | Elsevier |
| Document type | Article ; Online |
| Database | BASE - Bielefeld Academic Search Engine (life sciences selection) |
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