8^th European Immunology Conference

Biography

Biography: Mohammad Afzal Khan

Abstract

Microvascular loss is a major cause of chronic rejection in all solid organ transplants, and there are no ongoing immunosuppressive regimens sufficiently affect the restoration of functional microvascular flow during acute rejection [1]. Most immunotherapies for organ transplantation face the challenges of achieving enough immunosuppression to prevent organ rejection or limit autoreactivity without preserving microvasculature [2]. Tregs play a crucial role in maintaining immunological unresponsiveness to self-antigens and and secrete immunosuppressive IL-10 to suppress heightened immune responses destructive to the host tissue in organ transplant recipients [3], however, the effects of Treg mediated immunosuppression on microvascular reestablishment has been reported [4] but the molecular mechanism of Treg-mediated microvascular improvements has never been examined in rejecting allografts. To further demonstrate the role of IL-10, Balb/C→B6 allografts were treated with anti mouse IL-10 (10mg/kg, i.p. at d0 and every day thereafter), and allografts were monitored for Treg suppression, tissue oxygenation (tpO₂), blood perfusion and functional microvascular connections during allograft rejection. Our findings demonstrated that IL-10 blocking promotes induction of CD4⁺ T cells while suppress T regulatory cells, which favors accelerated microvascular loss and allograft rejection and as a consequence, tissue hypoxia, ischemia and associated airway remodeling after IL-10 blockade. Altogether, these findings suggested that targeted blocking of IL-10 trigger the induction of CD4⁺ T cells, which may confer key effector functions through inflammation and associated injuries. These findings may be useful in designing recombinant IL-10 based therapies to rescue tissue/organ rejection.