Vγ4 T细胞快速分泌IL-17分子机制及在皮肤移植免疫排斥反应中的作用研究

我们前期工作表明，皮肤移植后，Vγ4 T细胞激活后迅速大量产生IL-17并在移植物局部早期炎症的启动放大中发挥关键作用，进而加速皮肤移植免疫排斥反应。而Vγ4 T细胞激活后迅速大量产生IL-17是其在炎症早期发挥作用的关键前提基础，但相关分子机制目前尚未阐明。本课题拟围绕Vγ4 T细胞如何迅速大量产生IL-17这一关键科学问题，拟通过深入分析Vγ4 T细胞表达IL-17过程中NF-kB和STAT3信号通路所发挥的不同作用、关键核转录因子RORγt以及IL-17本身表达所涉及的表观遗传学特性，以阐明Vγ4 T细胞快速表达IL-17的具体分子机制。再通过模式动物体内明确这些机制在Vγ4 T细胞介导的皮肤移植排斥反应中的作用。从而实现我们对Vγ4 T细胞介导皮肤移植免疫排斥反应中的作用及相关分子机制比较完整深入的认知。

Our previous studies demonstrated that, upon skin graft transplantation, Vγ4 T cells were activated to rapidly produce large amount of IL-17, which played crucial roles in local inflammation to accelerate skin graft rejection. Rapid production of IL-17 by Vγ4 T cells was prerequisite for performing functions of Vγ4 T cells on inflammation. However, the underlying mechanisms of rapid IL-17 production by Vγ4 T cells upon stimulation still need to be clarified. In this study, we will analyze the roles of NF-kB and STAT3 signaling pathway play in inducing the expression of RORγt and IL-17, epigenetic character of RORγt and IL-17 gene promoter to demonstrate how Vγ4 T cells rapidly produce IL-17 upon stimulation.