THE FUNCTION OF T-BET IN T HELPER CELL DEVELOPMENT

T-BET 在辅助细胞发育中的作用

• 批准号: 6532634
• 负责人: STANFORD L. PENG
• 金额: $ 11.09万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6532634
• 关键词: cell differentiation; helper T lymphocyte; laboratory mouse; protein structure function; transcription factor

During ongoing immune responses, naive helper T precursor (Thp) cells differentiate into one of two lineages, Th1 or Th2, characterized by the expression of particular cytokines. This polarity mediates the balance between disease pathogenesis and suppression in several human conditions, including allergy; autoimmunity, and infection; however, the molecular basis of Th1 development remains largely unknown. Recently, a novel protein, T-bet (T-box expressed in T cells), has been isolated and found highly selective for Th1 cells, though it is also found in thymocytes, as well as NK and B cells. Interestingly, T-bet is a member of the T-box family of transcription factors, which have largely been implicated in embryonic development. Expression of this protein is sufficient to confer the Th1 phenotype upon both Thp and polarized Th2 cells, suggesting that it plays a substantial role in Th lineage commitment: This application proposes to analyze the biological function of T-bet by developing T-bet genetic mutant mice (Aim 1), identifying regulators and effectors of T-bet (Aim 2), and understanding its potential role in disease states (Aim 3).

在持续的免疫应答期间，初始辅助性T前体（Thp）细胞分化成两种谱系之一，Th 1或Th 2，其特征在于表达特定的细胞因子。 这种极性介导疾病的发病机制和抑制之间的平衡，在几个人的条件，包括过敏，自身免疫和感染;然而，Th 1发展的分子基础仍然在很大程度上是未知的。 最近，一种新的蛋白质，T-bet（T-box在T细胞中表达），已被分离和发现高度选择性的Th 1细胞，虽然它也被发现在胸腺细胞，以及NK和B细胞。 有趣的是，T-bet是转录因子T-box家族的成员，该家族在很大程度上与胚胎发育有关。 该蛋白质的表达足以赋予Thp和极化的Th 2细胞Th 1表型，表明其在Th谱系定型中起重要作用：本申请提出通过开发T-bet遗传突变小鼠（Aim 1）、鉴定T-bet的调节剂和效应物（Aim 2）以及理解其在疾病状态中的潜在作用（Aim 3）来分析T-bet的生物学功能。