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Artikel ; Online: 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

Cell Reports, Vol 22, Iss 5, Pp 1276-

2018  Band 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.
Schlagwörter thymus ; B cell ; aging ; Aire ; Biology (General) ; QH301-705.5
Thema/Rubrik (Code) 612
Sprache Englisch
Erscheinungsdatum 2018-01-01T00:00:00Z
Verlag Elsevier
Dokumenttyp Artikel ; Online
Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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