Models of Aire-Dependent Gene Regulation for Thymic Negative Selection

Models of Aire-Dependent Gene Regulation for Thymic Negative Selection

Mutations in the autoimmune regulator (AIRE) gene lead to autoimmune polyendocrinopathy syndrome type 1 (APS1), characterized by the development of multi-organ autoimmune damage. The mechanism by which defects in AIRE result in autoimmunity has been the subject of intense scrutiny. At the cellular level, the working model explains most of the clinical and immunological characteristics of APS1, ...

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...

Differential Features of AIRE-Induced and AIRE-Independent Promiscuous Gene Expression in Thymic Epithelial Cells.

Establishment of self-tolerance in the thymus depends on promiscuous expression of tissue-restricted Ags (TRA) by thymic epithelial cells (TEC). This promiscuous gene expression (pGE) is regulated in part by the autoimmune regulator (AIRE). To evaluate the commonalities and discrepancies between AIRE-dependent and -independent pGE, we analyzed the transcriptome of the three main TEC subsets in ...

Thymic T-Cell Education: Positive & Negative Selection

TOLERANCE (which is antigen-specific) must be distinguished from immune deficiency (non-specific). Its most important manifestation, the maintenance of SELFTOLERANCE, was originally explained by the Clonal Selection theory as the result of CLONAL ABORTION of self-reactive clones. However, potentially self-reactive Tand B-cells do exist in normal individuals, leading to the recognition of the im...

Negative Selection Timing and Casting for Actors of Thymic