Differential mechanisms for RORgammat-regulated thymocyte development and Th17 di

摘要 好了！ 为了成为有能力的效应者Th17细胞，介导实际的免疫反应，T 细胞必须依次经历两个依赖于RoR的分化过程 在胸腺和外周淋巴组织中进行。RoR？t被上调 胸腺细胞提高完成T细胞成熟过程所需的存活率 在胸腺中，缺乏ROR？t活性会严重损害胸腺细胞的发育， 最终会导致淋巴瘤。ROR？t在外周血中再次上调至 指导Th17细胞分化，介导多种类型的自身免疫。误差率？ 因此被认为是治疗Th17依赖的重要药物靶点 自身免疫力。然而，人们对这些共同而独特的机制知之甚少。 ROR？t用于调节这两个分化过程。我们的目标是了解 ROR？t在胸腺细胞和Th17细胞中的功能，这将促进 针对Th17依赖的自身免疫的药物，但不干扰 导致淋巴瘤的胸腺细胞发育。此应用程序的目标是 了解胸腺细胞和外周T细胞如何使用相同的 转录因子RoR？t调节它们的分化过程。

Abstract ! To become competent effector Th17 cells mediating the actual immune responses, T cells have to undergo two ROR¿t-dependent differentiation processes sequentially carried out in thymus and peripheral lymphoid tissues. ROR¿t is up-regulated in thymocyes to enhance the survival required for completion of T cell maturation process in thymus, and absence of ROR¿t activity severely impairs thymocyte development that eventually leads to lymphoma. ROR¿t is again up-regulated in peripheral CD4+ T cells to instruct the differentiation of Th17 cells that mediate many types of autoimmunity. ROR¿t is thus considered an important drug target for treatment of Th17-dependent autoimmunity. However, little is known about the common and distinct mechanisms that ROR¿t utilize to regulate these two differentiation processes. Our goal is to understand the function of ROR¿t in both thymocytes and Th17 cells, which will facilitate to develop drugs specifically targeting Th17-dependent autoimmunity, but not interfering with thymocyte development that leads to lymphoma. The objective of this application is to understand how both thymocytes and peripheral T cells differentially use the same transcription factor ROR¿t to regulate their differentiation processes.!