ICOS Expression Levels and Th Development

ICOS 表达水平和 Th 发展

• 批准号: 8221801
• 负责人: Rebecca A. Shilling
• 金额: $ 9.19万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 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/8221801
• 关键词: ICOS; Expression; Levels; Th; Development

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（由申请人提供）：本提案概述了一项为期 5 年的肺免疫生物学学术职业发展培训计划。主要研究者已在凯斯西储大学完成内科住院医师培训，并在芝加哥大学完成肺科和重症监护医学专科培训。她现在是芝加哥大学肺部和重症监护科的讲师。她将通过独特的细胞和分子免疫学项目扩展她的科学技能。该项目将促进细胞免疫学在哮喘、过敏等人类疾病基本免疫机制研究中的应用。 Anne Sperling 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者，也是一位杰出的导师，致力于将首席研究员发展成为独立的临床医生科学家。乔G.N.博士Garcia Garcia，Lowell T. Coggeshall 教授兼医学主席，一位成功培养了许多临床医生-科学家的杰出医师-研究员，将担任联合导师。他将提供学术和科学职业发展方面的专业知识。此外，由免疫学、肺生理学和分子生物学领域卓有成就的科学家组成的咨询委员会将为科学和职业发展做出贡献。 研究重点是诱导共刺激物 (ICOS) 表达水平的作用及其对 2 型辅助 T 细胞 (Th2) 分化的影响。最近实验室的工作表明ICOS是过敏致敏的易感基因，并表明ICOS的表达影响Th2分化和/或Th2效应功能。因此，该提案的总体假设是 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，ICOS 杂合子小鼠在过敏性气道疾病模型中具有较少的 Th2 分化和 Th2 介导的炎症。在本提案中，我将使用 ICOS 杂合子小鼠作为模型来了解 ICOS 定向 Th2 分化和 Th2 介导的气道炎症的机制。该提案的目标是进一步了解哮喘和过敏等疾病所涉及的免疫反应，这些疾病影响着美国和全世界数百万人。