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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：
9265772
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/9265772
关键词：
Alpha Cell Arthritis Autoimmune Diseases Autoimmunity Biological Process CD4 Positive T Lymphocytes Cell Differentiation process Cell Maturation Cells Chromatin Collaborations Data Development Diabetes Mellitus Drug Targeting Gene Expression Gene Targeting Goals Helper-Inducer T-Lymphocyte Immune response Impairment Interleukin-17 Lymphoid Tissue Lymphoma Mediating Modeling Molecular Profiling Multiple Sclerosis Orphan Pathologic Peripheral Pharmaceutical Preparations Play Process Proteins Recruitment Activity Regulation Role Signaling Molecule T cell regulation T cell transcription factor 1 T-Cell Development T-Lymphocyte Testing Therapeutic Thymic Lymphoma Thymocyte Development Thymus Gland Tretinoin Tumor stage Work beta catenin drug development epigenetic marker genome-wide analysis in vivo innovation mutant novel public health relevance receptor targeted treatment thymocyte tool transcription factor

项目摘要

DESCRIPTION (provided by applicant): To become competent effector Th17 cells mediating the actual immune responses, T cells have to undergo two RORγt-dependent differentiation processes sequentially carried out in thymus and peripheral lymphoid tissues. RORγt is up-regulated in thymocyes to enhance the survival required for completion of T cell maturation process in thymus, and absence of RORγt activity severely impairs thymocyte development that eventually leads to lymphoma. RORγt is again up-regulated in peripheral CD4+ T cells to instruct the differentiation of Th17 cells that mediate many types of autoimmunity. RORγt is thus considered an important drug target for treatment of Th17-dependent autoimmunity. However, little is known about the common and distinct mechanisms that RORγt utilize to regulate these two differentiation processes. Our goal is to understand the function of RORγt 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 RORγt to regulate their differentiation processes.

描述（由申请方提供）：为了成为介导实际免疫应答的有能力的效应Th17细胞，T细胞必须经历两个RORγ t依赖性分化过程，依次在胸腺和外周淋巴组织中进行。RORγt在胸腺细胞中上调，以提高完成胸腺中T细胞成熟过程所需的存活率，并且RORγt活性的缺失严重损害胸腺细胞发育，最终导致淋巴瘤。RORγt在外周CD4+ T细胞中再次上调，以指导介导多种类型自身免疫的Th17细胞的分化。因此，RORγt被认为是治疗Th17依赖性自身免疫的重要药物靶标。然而，RORγt调控这两个分化过程的共同和不同机制却知之甚少。我们的目标是了解RORγt在胸腺细胞和Th17细胞中的功能，这将有助于开发特异性靶向Th17依赖性自身免疫的药物，而不是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细胞如何不同地使用相同的转录因子RORγt来调节其分化过程。