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：
9696594
负责人：
SIMON Patrick HOGAN
金额：
$ 48.15万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
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/9696594
关键词：
Acute Adult Affect Allergens Allergic Allergic Reaction Anaphylaxis Antigen Presentation Antigens Cell secretion Cessation of life Child Clinical Communities Cyclic ADP-Ribose Dangerousness Dendritic Cells Development Diagnosis Disease Environment Environmental Risk Factor Epithelial Epithelium Exposure to Expressed Sequence Tags Family Food Food Hypersensitivity Food Labeling Genetic Genetic Predisposition to Disease Goblet Cells 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 Predisposing Factor Prevalence Process Proteins Quality of life Reaction Regulation Reporting Role Sampling Series Small Intestines Testing Th2 Cells Therapeutic Intervention Trees Visit cell type cholinergic clinical development clinically relevant crosslink cytokine defined contribution egg experimental study food allergen food antigen mast cell novel prevent psychologic public health relevance receptor response sensitizing antigen therapeutic development 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（由适用提供）：食物过敏是美国的一种严重而常见的疾病，被认为会影响4个家庭中的1个。食物过敏的主要批准疗法是避免食物。但是，随着在许多食物中使用牛奶，鸡蛋，花生和树坚果，通常不会预料到它们的存在，意外暴露和危险的暴露是常见的。最近，我们确定了一种新的肠道可溶性抗原采样机制，该机制是由Goblet细胞（GC）抗原通道（GAP）介导的10。在初步研究中，我们确定了GAP形成的调节中的新途径，并且在该途径的途径中，该途径在各种食物中均具有临床反应性和反应性的反应性促成的途径。我们的中心假设是，差距介导的“敏感食品过敏状态”的肠道抗原递送素料，并刺激对食物的临床反应性。该提案中概述的具体目的将直接涉及间隙形成在食品抗原表现的设施中，敏感食品过敏状态的发展以及对食物的临床反应性。关于预期的结果，预计提出的研究将证明：目标i）间隙是SI食品抗原递送到免疫系统的主要途径；目的ii）胆碱能诱导的差距通过增强食物抗原的递送来促进特征性易感性的“敏化食物过敏状态”；而瞄准III）与Mc衍生的IL-13紧邻GCS，与GCS紧邻gc，从而诱导了差距形成，从而增加了抗抗原的抗反应和促成的抗反应，提高了抗反应的反应。提出了促成的反应。我们目前对肠道腔抗原采样的潜在机制以及对食物的临床反应性的发展的理解，并确定差距是开发治疗干预措施的有吸引力的目标，以防止新食物过敏的发展。