Regulatory Role of Gama-Delta T cells in the Development of Pulmonary Fibrosis

描述(由申请人提供)： 这份提案描述了一项为期5年的培训计划，旨在发展肺科学、重症监护医学和免疫学的学术生涯。这位首席研究员在科罗拉多大学完成了肺和重症护理医学的结构化奖学金。他通过整合跨部门的资源来扩展他的科学技能。这项计划将促进对应用于肺部的免疫学的深入了解。丰特诺博士和奥布莱恩博士都将担任首席研究员科学发展的导师。丰特诺博士是一位在T细胞介导的肺部疾病方面备受推崇的专家。奥布莱恩博士是公认的v5T细胞研究的国际领导者。Fontenot博士和O‘Brien博士一起培养了许多临床科学家、博士后研究员和研究生。此外，一个咨询委员会，一个备受推崇的间质性肺病领域的科学家将提供科学和职业研究，将重点放在AP T细胞促进Y5 T淋巴细胞发展成肺纤维化的机制上。最近的实验室工作表明，小鼠反复吸入革兰氏阳性微生物枯草芽孢杆菌，会在肺和肺纤维化中产生大量的和Y5 T细胞。建议的实验旨在通过过继转移技术检测T细胞受体靶向缺失的转基因小鼠在肺纤维化发生中的作用。随后，将利用体内和体外细胞技术研究细胞亚群促进或延缓肺纤维化发展的机制。其具体目的包括：1.检测反复暴露于枯草杆菌的小鼠肺内AP T细胞是否促进沉积；2.阐明v5 T细胞在这种过敏性肺炎和肺纤维化模型中的免疫调节作用。这是科罗拉多大学和国家犹太医学研究中心通过其强大和综合的免疫学系，首次详细研究不同T细胞亚群在肺疾病发生中的作用，为年轻研究人员提供了一个肥沃的环境，从基础科学研究的最高水平开始建立独立的学术生涯。 (摘要结束)

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career Pulmonary Sciences, Critical Care Medicine and Immunology. The principal investigator has completed structured fellowship in Pulmonary and Critical Care Medicine at the University of Colorado. He expand his scientific skills through integration of interdepartmental resources. This program will promote the in-depth understanding of immunology as applied to pulmonary Drs. Fontenot and O'Brien will both serve as mentors for the principal investigator's scientific development. Dr. Fontenot is a highly regarded expert in T cell-mediated lung disease. Dr. O'Brien is recognized international leader in v5 T cell research. Together, Drs. Fontenot and O'Brien have trained numerous clinician scientists, postdoctoral fellows and graduate students. In addition, an advisory committee highly-regarded scientists in the fields of interstitial lung disease will provide scientific and career Research will focus on the mechanisms by which ap T cells promote while y5 T lymphocytes development of pulmonary fibrosis. Recent work in the laboratory has demonstrated that mice repeatedly inhale the Gram-positive microorganism, Bacillus subtilis, develop large numbers of and y5 T cells in the lung and pulmonary fibrosis. The proposed experiments are designed to examine role of each T cell subset in the generation of pulmonary fibrosis using adoptive transfer techniques transgenic mice with T cell receptor targeted deletions. Subsequently, the mechanisms by which cell subset promotes or delays the development of pulmonary fibrosis will be investigated using in vivo and vitro cellular techniques. The specific aims include: 1. Determe if ap T cells promote deposition in the lungs of mice repeatedly exposed to B. subtilis and 2. Delineate the immunoregulatory role of v5 T cells in this murine model of hypersensitivity pneumonitis and pulmonary fibrosis. This the first detailed investigation of the role of different T cell subsets in the generation of pulmonary The University of Colorado and National Jewish Medical Research Center through their strong and Integrated Department of Immunology provides young investigators a fertile environment to highest level of basic science research from which to build an independent academic career. (End of Abstract)