A novel model for dissecting roles of IL-17 in lung transplantation

The long-term success of lung transplantation is limited by the development of chronic lung allograft dysfunction (CLAD) in which IL-17 plays an important role. Direct evidence of IL-17-mediated allograft rejection has been observed when T-bet is absent. However, lack of T-bet also leads to failure in production of IFN-γ which is required for tolerance induction and allograft acceptance, as T-bet deficiency results in IL-17-expressing CD8+ T cells mediated costimulation blockade-resistant allograft rejection. Our previous research demonstrated that additional STAT6 deficiency to T-bet deficiency resulted in Th17-dominant immune responses, and importantly, restored IFN-γ production. Here we investigated whether T-bet/STAT6 double knout-out (DKO) mice as allograft recipients could provide a useful model to study IL-17 and Th17 in lung transplantation.