Novel tools to maximize profiling of tissue and antigen specific immune dysregulation in allergy and inflammatory bowel disesase

 描述（由申请人提供）：西奈山伊坎医学院（ISMMS）的人类免疫监测核心（HIMC）是一个由Merad博士及其同事于2011年牵头的新型研究中心，由ISMMS院长资助，旨在促进新型免疫分析工具的开发，以帮助识别诊断，预后和治疗反应的新型生物标志物。免疫系统研究的主要挑战之一是人类样本的有限性降低了我们对患者免疫功能进行深入全面分析的能力。本申请的目标是开发新型免疫分析工具和功能测定，以在两个临床领域（食物过敏和IBD）中鉴定疾病和对治疗的反应的新型靶标和新型生物标志物。最初对这两个疾病领域的关注反映了ISMMS对过敏性和IBD患者的非凡临床招募，但该资助中获得的任何技术发展将应用于其他炎症性疾病，如动脉粥样硬化和皮肤炎症性疾病，包括银屑病和特应性皮炎，ISMMS也是转诊中心。食物过敏是一种常见的儿童疾病，没有治疗或预防策略。ISMMS的儿科过敏和免疫学部门已经建立了该国最活跃的食物过敏临床研究项目之一。由于难以分析过敏原特异性细胞，特别是考虑到儿科患者可用的血容量小的挑战，机制见解落后于临床收益。因此，该提案的目标之一是开发新的免疫和基因组学工具，以在单细胞水平上识别和分析过敏原特异性T细胞。ISMMS炎症性肠病（IBD）中心在临床，遗传，微生物组和免疫学基础IBD研究的世界领导者之间的密切，综合合作方面是独一无二的。虽然探索致病的免疫调节剂的努力集中在利用GWAS数据和探索系统性失调，但很少有人致力于理解主要由于胃肠道组织的可用性有限而在组织部位发生的免疫失调的性质。因此，该项目的目标2提出利用ISMMS IBD中心获得的非凡组织样本开发新的免疫学测定法，以描述在早期诊断患者中以及在开始免疫调节剂后的不同时间浸润并促成IBD病变的免疫细胞区室。

 DESCRIPTION (provided by applicant): The human immune monitoring core (HIMC) at the Icahn School of Medicine at Mount Sinai (ISMMS) is a novel research center spearheaded by Dr. Merad and colleagues in 2011 and funded by the Dean of ISMMS to promote the development of novel immune profiling tools to help identify novel biomarkers of diagnosis, prognosis, and response to therapy. One of the main challenges to studies of the immune system has been the limited availability of human samples reducing our ability to perform in-depth comprehensive analysis of immune functions in patients. The goal of this application is to develop novel immune profiling tools and functional assays to identify novel targets and novel biomarker of diseases and response to therapy in two clinical areas: food allergy and IBD. The initial focus on these two disease areas reflects the extraordinary ISMMS clinical recruitment of allergic and IBD patients, yet any technological development obtained in this grant will be applied to other inflammatory disease such as atherosclerosis, and skin inflammatory disease including psoriasis and atopic dermatitis for which ISMMS is also a referral center. Food allergy is a common disease of childhood for which there are no treatment or prevention strategies. The Pediatric Allergy and Immunology division at ISMMS has built one of the most active clinical research programs in food allergy in the country. Mechanistic insights have lagged behind clinical gains due to the difficulty of profiling allergen-specific cells, particularly given the challenge of small blood volumes available from pediatric patients. Thus one of the goals of this proposal is to develop novel immune and genomics tools to identify and profile allergen-specific T cells at the single-cell level. The ISMMS Inflammatory Bowel Disease (IBD) Center is unique in its close, integrated collaborations between world-leaders in clinical, genetic, microbiome and immunology-based IBD research. While efforts to explore immune regulators causative of disease has focused on exploiting GWAS data and exploring systemic dysregulation, little effort has been devoted to comprehend the nature of the immune dysregulation that occurs at the tissue site mainly due to limited availability of gastrointestinal tissue. Thus Aim 2 of this projet proposes to leverage the extraordinary tissue samples obtained by the ISMMS IBD Center to develop novel immunological assays to profile immune cell compartments that infiltrate and contribute to IBD lesions in early diagnosed patients and at different time after initiation of immunodulatory agents.