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

点击翻译按钮获取中文摘要

 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.