The Role And Mechanism Of IRF4-BATF In T Cell-mediated Rejection

CHAPTER â… IRF4/BATF deficient Protects T cell-mediated RejectionInterferon regulatory factor4(IRF4)-Basic Leucine Zipper Transcription Factor, ATF-Like (BATF) are the transcription factor of effector T cells, which plays an important role in the differentiation of T cells. However the role of IRF4/BATF in the T cell-mediated acute rejection and memory rejection is not clear. In this section, we used IRF4/BATF deficient mouse to investigate the role of IRF4and BATF in mouse skin transplantation, heterotopic heart transplants and skin-heart transplantation model. The result showed that, graft-infiltrating T cells have high protein and mRNA level of IRF4and BATF. IRF4deficient will significantly prolong the survival of cardiac allograft by inhibiting the migration and cytokines production of effector T cells; in addition, IRF4knockout in T cells also protects the memory T cell-mediated Rejection. CHAPTER â…¡IRF4directly regulates the expression of PD-1In Chapter I, we have demonstrated that IRF4/BATF deficient Protects T cell-mediated Rejection. To study the mechanism, in this study, we investigated the role of IRF4and BATF in T cell metabolism, epigenetic regulation and costimulatory and co-inhibitor receptors expression. The results showed that, IRF4deficient affects the expression of T cell metabolism related molecules, and promotes the expression of co-inhibitor receptors, which PD-1protein and mRNA expression levels were significantly increased. Moreover, we used the retroviral transfection, CHIP-PCR and luciferase reporter assays to study how IRF4regulates the expression of PD-1. We found that IRF4inhibits the expression of PD-1by directly binding the upsteam promoter the PD-1, and IRF4cannot bind the upsteam of PD-1with the mutation binding site.