ICOS Expression Levels and Th Development

ICOS 表达水平和 Th 发展

• 批准号: 7146948
• 负责人: Rebecca A. Shilling
• 金额: $ 10.88万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7146948
• 关键词: asthma; career; emotions; genes; human; immune response; immunology; inflammation; medicine; model; proteins

DESCRIPTION (provided by applicant): A 5-year training program for the development of a career in academic pulmonary immunobiology is outlined in this proposal. The principal investigator has completed residency in internal medicine at Case Western Reserve University and a fellowship in pulmonary and critical care medicine at the University of Chicago. She is now an Instructor in the Section of Pulmonary and Critical Care, University of Chicago. She will expand upon her scientific skills through a unique program of cellular and molecular immunology. This program will promote command of the application of cellular immunology to the study of basic immune mechanisms of human diseases, such as asthma and allergy. Dr. Anne Sperling will mentor the principal investigators scientific development. She is a well-established investigator in cellular immunology and an outstanding mentor who is committed to the development of the principal investigator into an independent clinician-scientist. Dr. Joe G.N. Garcia, Garcia, the Lowell T. Coggeshall Professor and Chairman of Medicine, an outstanding physician-investigator who has successfully trained many clinician-scientists will serve as the Co-Mentor. He will provide expertise in academic and scientific career development. In addition, an advisory committee of accomplished scientists in immunology, pulmonary physiology and molecular biology will contribute to the scientific and career development. The research focus will be the role of Inducible Costimulator (ICOS) expression levels and its influence on T helper cell type 2 (Th2) differentiation. Recent work in the laboratory has demonstrated that ICOS is a susceptibility gene for allergic sensitization and suggest that the expression of ICOS affects Th2 differentiation and/or Th2 effector function. Thus the overall hypothesis of this proposal is that ICOS expression levels are directly associated with immune outcomes. I find that mice heterozygous for the ICOS gene express less surface ICOS than wild-type mice. My preliminary results demonstrate that ICOS heterozygous mice have less Th2 differentiation and Th2-mediated inflammation in a model of allergic airway disease. In this proposal, I will use ICOS heterozygous mice as a model to understand the mechanisms responsible for ICOS directed Th2 differentiation and Th2-mediated airway inflammation. The goal of this proposal is to further our understanding of the immune responses involved in diseases like asthma and allergy, which affect millions of people in the U.S. and worldwide.

描述(由申请者提供)：本提案概述了一项为期5年的培训计划，旨在发展学术肺免疫生物学的职业生涯。这位首席研究员已经在凯斯西储大学完成了内科住院医师资格，并在芝加哥大学获得了肺部和重症护理医学研究员资格。她现在是芝加哥大学肺和重症监护科的讲师。她将通过一个独特的细胞和分子免疫学项目来扩展她的科学技能。该计划将促进细胞免疫学在研究哮喘和过敏等人类疾病的基本免疫机制方面的应用。安妮·斯珀林博士将指导主要研究人员的科学发展。她是细胞免疫学领域的知名研究员和杰出的导师，致力于将首席研究员发展成为一名独立的临床医生和科学家。Lowell T.CoggesHall教授兼医学主席Joe G.N.Garcia博士将担任共同导师，他是一位成功培养了许多临床医生和科学家的杰出的医生和研究员。他将提供学术和科学职业发展方面的专业知识。此外，一个由免疫学、肺部生理学和分子生物学方面的杰出科学家组成的咨询委员会将为科学和职业发展做出贡献。 研究的重点将是诱导共刺激分子(ICOS)表达水平的作用及其对辅助性T细胞2型(Th2)分化的影响。最近的实验室工作表明，ICOS是变态反应性致敏的易感基因，提示ICOS的表达影响Th2分化和/或Th2效应器功能。因此，这一建议的总体假设是，ICOS表达水平与免疫结果直接相关。我发现ICOS基因杂合子的小鼠比野生型小鼠表达更少的表面ICOS。我的初步结果表明，在过敏性呼吸道疾病模型中，ICOS杂合子小鼠的Th2分化和Th2介导的炎症较少。在这项提案中，我将使用ICOS杂合子小鼠作为模型，以了解ICOS诱导Th2分化和Th2介导的呼吸道炎症的机制。这项提案的目的是加深我们对哮喘和过敏等疾病所涉及的免疫反应的理解，这些疾病影响着美国和世界各地数百万人。