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）：该提案中概述了一项为期5年的学术肺免疫生物学事业的培训计划。首席研究人员已完成凯斯西部储备大学内科住院医师的住院医师，并在芝加哥大学获得了肺和重症监护医学研究金。她现在是芝加哥大学肺和重症监护区的教练。她将通过独特的细胞和分子免疫学计划来扩展自己的科学技能。该程序将促进细胞免疫学在研究人类疾病基本免疫机制（例如哮喘和过敏的基本免疫机制的研究）中的指挥。安妮·斯佩林（Anne Sperling）博士将指导主要研究人员科学发展。她是一位良好的细胞免疫学研究者，也是一位杰出的导师，他致力于将主要研究人员发展成独立的临床医生 - 科学家。 Joe G.N.博士加西亚（Garcia），加西亚（Garcia），洛厄尔（Lowell T.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，肺部生理学和分子生物学的有成就科学家的咨询委员会将有助于科学和职业发展。 研究重点将是诱导型共刺激剂（ICO）表达水平及其对T辅助细胞2型（TH2）分化的影响。实验室中的最新工作表明，ICOS是过敏敏化的易感基因，并表明ICOS的表达会影响Th2分化和/或TH2效应子功能。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基因的杂合子比野生型小鼠表达的表面ICOS少。我的初步结果表明，在过敏性气道疾病模型中，ICO杂合小鼠具有较小的Th2分化和Th2介导的炎症。在此提案中，我将使用ICO杂合小鼠作为模型来了解导致ICO的TH2分化和Th2介导的气道炎症的机制。该提案的目的是进一步了解哮喘和过敏等疾病涉及的免疫反应，这影响了美国和全球数百万人。