Role of Lung Inflammation in Th2 Priming

描述(由申请者提供)：本建议书描述了一项为期5年的过敏和免疫学学术生涯发展培训计划。这位首席研究员在坦普尔大学完成了医学博士学位，在耶鲁大学医学院完成了内科住院医师培训，目前正在同一研究所完成过敏和临床免疫学奖学金。这项计划将允许候选人扩展她以前的科学技能，并在哮喘发病机制和Th2激发领域变得熟练。金博特利博士将指导首席研究员的科学发展。博托姆利博士是哮喘发病机制领域公认的领导者。博托姆利博士是一名免疫生物学教授，成功地培养了许多博士后研究员和研究生。研究将集中在Th2炎症影响初始的CD4T细胞对新的环境抗原的启动的机制。这一过程的发生机制不同于在幼鼠体内启动Th2的机制，而且可能独立于先天免疫系统而发生。我们的初步数据显示，炎症过程中产生的Th2细胞因子导致了新的Th2效应细胞群的启动。具体目的包括：1)研究IL-4在该模型中的作用。2)识别IL-4作用的靶细胞。3)研究IL-13的作用并鉴定IL-13作用的细胞。哮喘在发达国家是一种日益流行的疾病，对发病率和死亡率有巨大影响。如果我们了解了发病机制，我们将能够将其应用于患者护理。我们希望学习足够的知识，在哮喘发展之前预防它。这一K08奖项将极大地帮助候选人研究哮喘的发病机制和炎症机制，并为她提供时间和资源，使她发展成为一名熟练的独立研究员。

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career in Allergy and Immunology. The principal investigator has completed an M.D. at Temple University, residency training in Internal Medicine at Yale University School of Medicine and is currently completing an Allergy and Clinical Immunology fellowship at the same institute. This program will allow the candidate to expand on her previous scientific skills and to become proficient in the fields of asthma pathogenesis and Th2 priming. Dr. Kim Bottomly will mentor the principal investigator's scientific development. Dr. Bottomly is a recognized leader in the field of asthma pathogenesis. Dr. Bottomly is a Professor of Immunobiology and has successfully trained numerous postdoctoral fellows and graduate students. Research will focus on the mechanisms by which Th2 inflammation affects priming of naive CD4 T cells to new environmental antigens. This process occurs by a mechanism distinct from that responsible for Th2 priming in a naive mouse and may occur independently from the innate immune system. Our preliminary data show Th2 cytokines produced during inflammation lead to priming of a new population of Th2 effector cells. The specific aims include: 1) investigation of the role of IL-4 in this model. 2) identification of the target cell upon which IL-4 acts. 3) investigation of the role of IL-13 and identification of the cell upon which IL-13 acts. Asthma is a growing epidemic in developed nations with a huge impact in morbidity and mortality. If we understand the pathogenesis we will be able to apply this to patient care. Our hope is to learn enough to prevent asthma before it develops. This K08 award will greatly assist the candidate's research into asthma pathogenesis and mechanisms of inflammation and provide her with time and resources to develop into a skilled independent investigator.