ICOS Expression Levels and Th Development

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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.