ICOS Expression Levels and Th Development

描述（由申请人提供）：本提案概述了一个为期5年的培训计划，用于发展学术肺免疫生物学职业。主要研究者在凯斯西储大学完成了内科住院医师培训，并在芝加哥大学获得了肺部和重症监护医学奖学金。她现在是芝加哥大学肺部和重症监护科的讲师。她将通过细胞和分子免疫学的独特计划扩展她的科学技能。该项目将促进细胞免疫学在人类疾病（如哮喘和过敏）的基本免疫机制研究中的应用。安妮·斯珀林博士将指导主要研究者的科学发展。她是细胞免疫学方面的一位成熟的研究者，也是一位杰出的导师，致力于将主要研究者发展成为一名独立的临床科学家。Joe G.N.博士加西亚，加西亚，洛厄尔·T科格斯霍尔教授和医学主席，一位杰出的医生，研究者谁成功地培养了许多临床医生，科学家将担任共同导师。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、肺生理学和分子生物学领域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（Th 2）分化的影响。最近的实验室工作已经证明，ICOS是过敏性致敏的易感基因，并表明ICOS的表达影响Th 2分化和/或Th 2效应子功能。因此，该提议的总体假设是ICOS表达水平与免疫结果直接相关。我发现ICOS基因杂合的小鼠比野生型小鼠表达更少的表面ICOS。我的初步研究结果表明，ICOS杂合子小鼠在过敏性气道疾病模型中具有较少的Th 2分化和Th 2介导的炎症。在这个建议中，我将使用ICOS杂合子小鼠作为模型，以了解负责ICOS指导的Th 2分化和Th 2介导的气道炎症的机制。这项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世界各地数百万人。

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.