University of Louisville, USA
Title: Mechanistic basis of allotolerance induced by SA-FasL-engineered pancreatic islets
Biography: Haval Shirwan
We have recently shown that pancreatic islets engineered to display on their surface a novel form of FasL induce robust allotolerance. Tolerance is initiated by direct targeting of alloreactive pathogenic T effector cells with upregulated expression of Fas receptor for physical elimination through activation-induced cell death. The apoptotic process initiates a cascade of immunoregulatory mechanisms that involve phagocytes, TGF-β, and CD4+CD25+FoxP3+ Treg cells. Treg cells are not only critical to the induction but also maintenance of tolerance. This talk will focus on extensive discussion of these mechanisms and implication of this novel immunomodulatory approach for altering the balance between T effector and Treg cells with potential application to graft rejection and autoimmune diseases where a favorable balance for Treg cells has therapeutic potential.