Degrading View of Immune Tolerance Dr Shoba Amarnath, Newcastle University
CD4+ Regulatory T cells (Tregs) are vital for maintaining immune tolerance and are characterised by the expression of the master transcription factor FoxP3. FoxP3 protein expression and stability is crucial for Treg cell function. Therefore, understanding the regulation of Foxp3 will add valuable knowledge towards developing novel therapeutics against autoimmune diseases.
Dr Armarnath's laboratory we have demonstrated that a protease known as asparaginyl endopeptidase (AEP) is expressed by murine Tregs. AEP directly targets FoxP3 protein, in iTregs, for degradation and blocking AEP enhances the stability of Foxp3 protein. Furthermore, we found that AEP is regulated by co-receptor signalling in iTregs. Specifically, the coinhibitory receptor programmed cell death -1 (PD-1) significantly inhibits AEP expression in murine Tregs thereby regulating FoxP3 stability in iTregs.