Mechanistic Core

机制核心的主要目标是：1)继续之前授权期的机制研究，旨在确定食物过敏和“自然”或免疫治疗诱导耐受发展的机制；2)为新提案中的每个项目提供一个平台，以实现这些目标；3)利用在初始授权期收集的信息建立新的假设，并为调查提供新的途径。在最初的批准期间，我们在5个位点建立了统一的可重复技术，允许研究致敏性和t细胞活化，并评估耐受性的发展。有几项发现使我们对之前的一些教条提出了质疑，包括大量对牛奶和鸡蛋过敏的儿童在很小的时候就已经对花生过敏，GATA-3转录因子在人类过敏致敏中的作用可能比以前认为的要小，这些患者中IL-4（以及随后的IgE）的非T细胞来源的可能性很大。目前的提案旨在继续

The broad goals of the Mechanistic Core are the following: 1) to continue mechanistic studies from the prior granting period aimed at defining the mechanisms underlying the development of food allergy and "natural" or immunotherapeutically-induced tolerance, 2) to provide a platform for every project within this new proposal to achieve these goals and 3) to utilize the information gathered during the initial granting period to establish new hypotheses and provide new avenues for investigation. During the initial granting period we established uniform reproducible technology across 5 sites allowing for the study of sensitization and T-cell activation, and assessment of the development of tolerance. There were several findings that caused us to question some of the previous dogma including the fact that a large cohort of milk and egg allergic children were already sensitized to peanut at an early age, that the GATA-3 transcription factor may play less of a role in allergic sensitization in humans than previously thought and that there was a high likelihood of a non- T cell origin for IL-4 (and consequent IgE) in these patients. The current proposal seeks to continue the current studies focused on the role of T cells vs. APCs in allergic sensitization and tolerance, as well as expand studies on the role of basophils in this process. In addition, we now plan to specifically explore the expression and regulation of GATA-3 in T and non-T cells, initiate studies attempting to correlate the expression of food allergy as either atopic, i.e. atopic dermatitis, asthma or allergic rhinitis, vs eosinophilic esophagitis using the immunologic parameters previously described, and finally to use a microarray approach to define novel pathways and markers of atopic disease, disease resolution and tolerance and the distinct expression of disease phenotypes (AD vs EE). These ongoing and new studies should enhance our understanding of the pathogenesis of atopic disease based upon human study.