Haval Shirwan
University of Louisville, USA
Title: Apoptosis as an effective means of inducing tolerance to pancreatic islets for the treatment of type 1 diabetes
Biography
Biography: Haval Shirwan
Abstract
Type 1 diabetes (T1D) is an autoimmune disease initiated and perpetuated by T cells targeting various autoantigens expressed by insulin producing beta cells, thereby setting off a serious of immunological reactions that result in the destruction of beta cells, insulin deficiency, and hyperglycemia. Insulin treatment as standard of care is often ineffective in preventing recurrent hyperglycemic episodes with subsequent development of micro and macroangiopathic lesions and the development and progression of chronic complications. Pancreatic islet transplantation has proven effective in improving metabolic control/quality of life and preventing severe hypoglycemia in patients with T1D. Immune rejection, however, severely limits broad application of islet transplantation, irrespective of chronic use of immunosuppression and its sequelae. Therefore, novel approaches that control rejection in the absence of chronic immunosuppression will have significant impact on the field of islet transplantation. T-cells are the primary culprit of islet graft rejection. As such, control of T cell responses has the potential to induce tolerance and treatment of T1D. T cells upregulate Fas receptor and become sensitive to Fas/FasL-mediated killing. Therefore, Fas-mediated apoptosis has great potential to serve as an effective means of inducing transplantation tolerance. Using a novel form of FasL protein with improved apoptotic activity, we have demonstrated the utility of this concept for the induction of tolerance to allogeneic as well as xenogeneic pancreatic islets in preclinical rodent experimental models.
