Aire mediates thymic expression and tolerance of pancreatic antigens via an unconventional transcriptional mechanism
Dina Danso-Abeam, Kim A Staats, Dean Franckaert, Ludo Van Den Bosch, Adrian Liston, Daniel HD Gray, James Dooley
European Journal of Immunology | WILEY | Published : 2013
The autoimmune regulator (Aire), mediates central tolerance of peripheral self. Its activity in thymic epithelial cells (TECs) directs the ectopic expression of thousands of tissue-restricted antigens (TRAs), causing the deletion of autoreactive thymocytes. The molecular mechanisms orchestrating the breadth of transcriptional regulation by Aire remain unknown. One prominent model capable of explaining both the uniquely high number of Aire-dependent targets and their specificity posits that tissue-specific transcription factors induced by Aire directly activate their canonical targets, exponentially adding to the total number of Aire-dependent TRAs. To test this "Hierarchical Transcription" m..View full abstract
Awarded by NH&MRC Project Grant
Awarded by NH&MRC Career Development Fellowship
We would like to gratefully acknowledge Dr. A. Farr for the provision of hybridoma clones. This work was funded by grants from the VIB and FWO and an NH&MRC Project Grant (no. 637332). D. H. D. G was supported by an NH&MRC Career Development Fellowship (no. 637353). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NH&MRC IRI-ISS. A. L. was supported by a JDRF Career Development Award. D.D-A. was supported by an IRO fellowship.