IRF4-dependent T-cell effector programs in governing transplant outcomes

项目摘要 实体器官移植是终末期器官衰竭患者的一种挽救生命的治疗方法，但 同种异体移植物的长期存活受到免疫排斥和免疫抑制药物副作用的限制。 同种异体T细胞反应对移植结果(排斥反应与耐受性)至关重要。它是这样的 对确定影响移植结果的T细胞效应器程序至关重要。 我们最近发现干扰素调节因子4(IRF4)是一个关键的转录决定因素 控制移植中的同种异体T细胞反应。T细胞中IRF4缺失导致进行性 建立CD4+T细胞功能障碍与同种异体心脏移植物长期存活这些发现有 已被接受以豁免权发表。在这里，我们假设IRF4管理移植 通过控制T细胞功能的核心调节电路的结果。因此，中心焦点 这项建议的目的是确定同种异体反应性效应器T细胞中IRF4控制的调节电路。

Project Summary Solid organ transplantation is a lifesaving treatment for patients with end-stage organ failure, but long- term allograft survival is limited by immune rejection and side effects of immunosuppressive drugs. Allogeneic T cell responses are central to transplant outcomes (rejection versus tolerance). It is thus essential to define the T cell effector programs that affect the transplant outcomes. We recently discovered that interferon regulatory factor 4 (IRF4) is a key transcriptional determinant controlling allogenic T cell response in transplantation. IRF4 deletion in T cells results in progressive establishment of CD4+ T cell dysfunction and long-term cardiac allograft survival. These findings have been accepted for publication in Immunity. Herein, we hypothesized that IRF4 governs transplant outcomes through controlling the core regulatory circuits of T cell function. Therefore, the central focus of this proposal is to identify the IRF4 controlled regulatory circuits in alloreactive effector T cells.