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Differential mechanisms for RORgammat-regulated thymocyte development and Th17 di

RORgammat 调节胸腺细胞发育和 Th17 di 的差异机制

基本信息

批准号：
8635224
负责人：
Zuoming Sun
金额：
$ 42万
依托单位：
BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8635224
关键词：
Affect Arthritis Autoimmune Diseases Autoimmunity Biological Process CD4 Positive T Lymphocytes Cell Maturation Cells Chromatin Collaborations Data Development Diabetes Mellitus Drug Targeting Gene Expression Gene Targeting Goals Helper-Inducer T-Lymphocyte Immune response Interleukin-17 Lymphoid Tissue Lymphoma Mediating Modeling Molecular Profiling Multiple Sclerosis Orphan Peripheral Pharmaceutical Preparations Play Process Proteins Recruitment Activity Regulation Role Signal Transduction Signaling Molecule Staging T cell differentiation T cell transcription factor 1 T-Cell Development T-Lymphocyte Testing Therapeutic Thymic Lymphoma Thymocyte Development Thymus Gland Tretinoin Work drug development epigenetic marker genome-wide in vivo innovation mutant novel public health relevance receptor thymocyte tool transcription factor

项目摘要

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.!

摘要 ! 为了成为有能力的效应Th17细胞介导实际的免疫应答，T 细胞必须依次经历两个依赖ROR t的分化过程在胸腺和外周淋巴组织中进行。ROR t在以下情况下上调：胸腺细胞的生存，以提高完成T细胞成熟过程所需的在胸腺中，ROR t活性的缺乏严重损害胸腺细胞的发育，最终导致淋巴瘤ROR t在外周CD4+ T细胞中再次上调，指导介导多种类型自身免疫的Th17细胞的分化。滚吧因此被认为是治疗Th17依赖性自身免疫然而，人们对这些共同和独特的机制知之甚少， ROR不能用来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，这将有助于发展特异性靶向Th17依赖性自身免疫但不干扰胸腺细胞发育导致淋巴瘤本申请的目的是了解胸腺细胞和外周T细胞如何区别使用相同的转录因子ROR？t来调节它们的分化过程。