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年的学术肺免疫生物学职业发展培训计划。首席研究员在凯斯西储大学完成了内科住院实习，并在芝加哥大学获得了肺病和重症监护医学的奖学金。她现在是芝加哥大学肺科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人类疾病（如哮喘和过敏）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，致力于将首席研究者发展成为独立的临床科学家。Joe G.N. Garcia博士，是Lowell T. Coggeshall教授和医学主席，是一位杰出的医师调查员，他成功地培训了许多临床科学家，他将担任联合导师。他将在学术和科学事业发展方面提供专业知识。此外，一个由免疫学、肺生理学和分子生物学领域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。

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.