Role of Lung Inflammation in Th2 Priming

描述（由申请人提供）：本提案描述了过敏和免疫学学术生涯发展的5年培训计划。首席研究员在天普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。该计划将允许候选人扩展她以前的科学技能，并成为精通哮喘发病机制和Th2启动领域。Kim Bottomly博士将指导首席研究员的科学发展。Bottomly博士是哮喘发病机理领域公认的领导者。Bottomly博士是免疫生物学教授，并成功培养了许多博士后研究员和研究生。研究将集中于Th2炎症影响初始CD4 T细胞对新环境抗原的启动机制。这一过程发生的机制不同于幼稚小鼠中负责Th2启动的机制，可能独立于先天免疫系统发生。我们的初步数据显示，在炎症过程中产生的Th2细胞因子导致启动一个新的Th2效应细胞群。具体目的包括：1)研究IL-4在该模型中的作用。2)鉴定IL-4作用的靶细胞。3)研究IL-13的作用和鉴定IL-13作用的细胞。在发达国家，哮喘是一种日益严重的流行病，对发病率和死亡率有着巨大的影响。如果我们了解了发病机制，我们就能将其应用于患者护理。我们的希望是了解到足够的信息，在哮喘发展之前预防它。此次获得K08奖将极大地帮助候选人对哮喘发病机制和炎症机制的研究，并为她发展成为一名熟练的独立研究者提供时间和资源。

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.