Pathways Regulating Lung Transplant Tolerance

PROJECT SUMMARY / ABSTRACT Lung transplantation, the only available therapy for many patients who suffer from end-stage pulmonary failure, continues to be plagued by disappointing long-term survival rates. Our research suggests that the premature demise of many transplanted lungs is in large part due to the use of immunosuppression that is not tailored towards the unique immunological characteristics of this organ. Our work will identify cellular and molecular pathways that can be targeted to prevent rejection and promote tolerance after lung transplantation. To accomplish this goal, we will utilize clinically relevant mouse models of lung transplantation, relevant conditional knockout strains and intravital imaging platforms to examine how local and peripheral immune pathways protect lung grafts from destruction by recipient immune cells. Our three projects are entitled “Local and peripheral mechanisms of T cell-mediated immune regulation after lung transplantation” (Project 1), “Early and late inflammatory events controlling lung allograft homeostasis” (Project 2) and “Targeting and imaging of inflammatory circuits in CLAD” (Project 3). The program project will be supported by a Microsurgery Core and an Administrative Core. Our proposed experiments will yield new information that will result in the development of lung-specific therapies that will improve outcomes for pulmonary transplant recipients.