IMMUNOLOGICAL REGULATION OF CHRONIC AIRWAY INFLAMMATION

慢性气道炎症的免疫调节

• 批准号: 6616338
• 负责人: NIGEL Patrick KILLEEN
• 金额: $ 14.27万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6616338
• 关键词: Mycoplasma; T cell receptor; T lymphocyte; angiogenesis; bronchus circulation; genetically modified animals; immunoregulation; inflammation; laboratory mouse; lymphocyte proliferation; mycoplasmal pneumonia; respiratory epithelium; respiratory hypersensitivity; respiratory infections; tissue /cell culture; tumor necrosis factor alpha

This project addresses immunological mechanisms that regulate chronic inflammation and remodeling in the respiratory tract. Mycoplasma pulmonis infection induces lifelong reorganization of the airway vasculature and mucosal epithelium and is a murine model of human chronic airway inflammation. Preliminary data suggest that M. pulmonis-related airway remodeling is regulated by T lymphocytes. The experiments in this proposal are designed to determine the mechanisms by which T cells regulate changes in the airways. The T cell response to M. pulmonis will be characterized and tested for its capacity to influence different aspects of airway remodeling. M. pulmonis-reactive T cells will be studied at the level of T cell receptor repertoire, cytokine phenotype and ability to induce immunopathology. Experiments will also address the physiological function of CD134, a member of the Tumor necrosis family of receptors that is prominently expressed on inflammatory T cells and which regulates the proliferation of T cells. These last experiments will focus on determining the mechanism by which CD134 influences T cell expansion and uncovering the circumstances in which CD134 function is most significant. These experiments will provide basic information about immunological mechanisms that influence the form and extent of airway remodeling in chronic airway inflammatory diseases. A better understanding of these mechanisms may suggest novel therapeutic targets and approaches for treating chronic airway disease.

该项目解决了调节呼吸道中慢性炎症和重塑的免疫机制。 支原体肺部感染诱导气道脉管系统和粘膜上皮的终生重组，是人类慢性气道炎症的鼠模型。初步数据表明，肺部与肺部相关的气道重塑受T淋巴细胞调节。 该提案中的实验旨在确定T细胞调节气道变化的机制。 T细胞对肺杆菌的反应将被表征并测试其影响气道重塑不同方面的能力。 肺部反应性T细胞将在T细胞受体库，细胞因子表型和诱导免疫病理学的能力上进行研究。实验还将解决CD134的生理功能，CD134是受体肿瘤坏死家族的成员，在炎症T细胞上显着表达，并调节T细胞的增殖。 这些最后的实验将着重于确定CD134影响T细胞扩展并发现CD134功能最重要的情况的机制。 这些实验将提供有关影响慢性气道炎症性疾病中气道重塑形式和程度的免疫机制的基本信息。 更好地了解这些机制可能表明新的治疗靶标和治疗慢性气道疾病的方法。