Food Allergy and Goblet Cell Antigen Passages

食物过敏和杯状细胞抗原通道

基本信息

批准号：
9063080
负责人：
SIMON Patrick HOGAN
金额：
$ 49.45万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-04 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9063080
关键词：
Acute Adult Affect Allergens Allergic Allergic Reaction Anaphylaxis Antigen Presentation Antigens Cell secretion Cells Cessation of life Child Clinical Communities Cyclic ADP-Ribose Dendritic Cells Development Diagnosis Disease Emergency department visit Environment Environmental Risk Factor Epithelial Epithelium Exposure to Family Figs - dietary Food Food Hypersensitivity Food Labeling Genetic Genetic Predisposition to Disease Goblet Cells Health Human IgE Immune response Immune system Immunology Individual Interleukin-13 Intestines Knowledge Lamina Propria M cell Mediating Mediator of activation protein Medical Milk Mus Muscarinics Nutritional Nuts Oral Outcome Study Parents Pathway interactions Prevalence Process Proteins Quality of life Reaction Regulation Reporting Role Sampling Series Small Intestines Testing Th2 Cells Therapeutic Intervention Trees base cell type cholinergic clinically relevant crosslink cytokine defined contribution egg food allergen food antigen novel prevent psychologic receptor research study response treatment adherence

项目摘要

DESCRIPTION (provided by applicant): Food allergy is a serious and common disorder within the U.S. and is thought to impact 1 in 4 families. The main approved therapy for food allergy is food avoidance; however, with the use of milk, eggs, peanuts and tree nuts in many foods in which their presence might not normally be anticipated, accidental and dangerous exposures are common. Recently, we identified a new mechanism of intestinal luminal soluble antigen sampling, which was mediated by goblet cell (GC) antigen passages (GAPs) 10. In preliminary studies, we identified a new pathway in the regulation of GAP formation and an important role for this pathway in atopic susceptible mice in both the development of clinical reactivity to foods and onset of an acute food allergic reaction. Our central hypothesis is that GAP-mediated intestinal antigen delivery primes for the "sensitized food allergic state" and stimulates clinical reactivity to foods. The Specific Aims outlined in this proposal will directly est the involvement of GAP formation in the facilitation of food antigen presentation, development of the sensitized food allergic state and clinical reactivity to foods. With respect to the expected outcomes, the studies proposed are expected to demonstrate that: Aim I) GAPs are the primary pathway of SI food antigen delivery to the immune system; Aim II) that cholinergic-induced GAPs promote the "sensitized food allergic state" in atopic susceptible" individual by enhancing the delivery of food antigens; and Aim III) MC-derived IL- 13 in close proximity to GCs induces GAP formation, thereby augmenting antigen delivery and onset of a food- induced anaphylactic reaction. Successful completion of the proposed studies will provide a new and substantive departure from our current understanding of the underlying mechanisms of intestinal luminal antigen sampling and development of clinical reactivity to foods and identify GAPs as an attractive target for the development of therapeutic intervention to prevent development of new food allergies.

描述（由申请人提供）：食物过敏是美国一种严重且常见的疾病，被认为影响四分之一的家庭。批准的主要食物过敏疗法是避免食用牛奶、鸡蛋、花生。和坚果在许多食物中的存在通常是不可预见的，但意外和危险的暴露是常见的。最近，我们发现了一种由杯状细胞介导的肠腔可溶性抗原采样的新机制。 (GC) 抗原通道 (GAP) 10. 在初步研究中，我们发现了一种调节 GAP 形成的新途径，并且该途径在特应性易感小鼠中在对食物的临床反应性的发展和急性急性过敏反应的发生中发挥着重要作用。我们的中心假设是，GAP 介导的肠道抗原传递引发“致敏食物过敏状态”并刺激对食物的临床反应。促进食物抗原呈递、致敏食物过敏状态和对食物的临床反应性的发展。就预期结果而言，拟议的研究预计将证明：目标 I) GAP 是 SI 食物抗原递送至人体的主要途径。免疫系统；目标 II) 胆碱能诱导的 GAP 通过增强食物抗原的传递，促进特应性易感个体的“致敏食物过敏状态”；目标 III) MC 衍生的 IL- 13 靠近 GC 会诱导 GAP 形成，从而增强抗原递送和食物引起的过敏反应的发生，拟议研究的成功完成将为我们目前对肠腔抗原采样的基本机制的理解提供新的实质性偏离。和对食物的临床反应的发展，并将 GAP 确定为开发治疗干预措施以预防新食物过敏的一个有吸引力的目标。