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: 6166268
• 负责人: STANFORD L. PENG
• 金额: $ 11.26万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 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/6166268
• 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).

在持续的免疫反应中，幼稚的辅助T细胞前体(THP)细胞分化为两个谱系之一，Th1或Th2，其特征是表达特定的细胞因子。这种极性在几种人类状况下调节疾病发病和抑制之间的平衡，包括过敏、自身免疫和感染；然而，Th1发育的分子基础在很大程度上仍不清楚。最近，一种新的蛋白T-bet(T-box在T细胞中表达)被分离出来，并发现它对Th1细胞具有高度的选择性，但它也存在于胸腺细胞以及NK和B细胞中。有趣的是，T-bet是T-box转录因子家族的成员，该家族在很大程度上与胚胎发育有关。该蛋白的表达足以赋予THP和极化的Th2细胞Th1表型，表明它在Th谱系承诺中发挥着重要作用：本应用旨在通过开发T-bet基因突变小鼠(目标1)、识别T-bet的调节因子和效应器(目标2)以及了解其在疾病状态中的潜在作用(目标3)来分析T-bet的生物学功能。