The pig: A novel large animal model of allergic eosinophilic esophagitis

猪：一种新型的过敏性嗜酸粒细胞性食管炎大型动物模型

• 批准号: 10092945
• 负责人: Tobias E Kaeser
• 金额: $ 19.43万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092945
• 关键词: Adolescent; Adult; Affect; Age; Allergens; Allergic; Allergic Disease; Allergy to eggs; Anatomy; Animal Model; Applied Research; Basic Science; Biological; Biopsy; Blood specimen; Cells; Child; Chronic; Clinical; Clinical Treatment; Collaborations; Complex; Deglutition Disorders; Development; Diagnosis; Diagnostic Procedure; Diagnostic tests; Disease; Dose; Early Diagnosis; Egg White Proteins; Endoscopy; Environment; Eosinophilic Esophagitis; Epithelial; Esophageal Stenosis; Esophageal mucous membrane; Esophagus; Event; FDA approved; Family suidae; Fibrosis; Food; Food Hypersensitivity; Funding; Gastrointestinal tract structure; Gland; Goals; Health; Human; Immune; Immune response; Immune system; Immunologics; Immunologist; Immunology; Incidence; Infiltration; Inflammation; Ingestion; Knowledge; Label; Medical; Mission; Modeling; Molecular; Monitor; Mus; National Institute of Allergy and Infectious Disease; Oral; Ovalbumin; Pain; Pathogenicity; Pathologic; Pathology; Pharyngeal structure; Physicians; Population; Prevalence; Production; Proteins; Public Health; Reaction; Research; Research Support; Science; Scientist; Side; Solid; Steroids; Swelling; Symptoms; T-Cell Activation; Testing; Time; Tissue Sample; Training; Translational Research; United States National Institutes of Health; Universities; Veterinary Medicine; Visualization; Withdrawal; allergic response; base; chemokine; clinical Diagnosis; college; cost; cytokine; disability; egg; eosinophil; experimental study; gastrointestinal; improved; medical schools; mouse model; new therapeutic target; novel; novel diagnostics; porcine model; prevent; research clinical testing; response; tool; translational model; treatment response

Food allergy is an increasing health problem with impacts on both children and adults. Despite the increasing impact of food allergy on human health and the US economy ($25B in children alone) and extensive research efforts, there is still no cure for food allergies. One of the devastating symptoms of food allergies is a disorder known as eosinophilic esophagitis (EoE) where the reaction to foods causes severe inflammation in the esophagus (throat). The swelling is painful and prevents the ingestion of solid foods. Children and adults of any age can develop EoE; children can fail to thrive, and EoE can progress in adolescents and adults to esophageal strictures which cause dysphagia and food impaction. In this proposal funds are requested to develop a new, translational, large animal model for EoE. We propose using young, food allergic pigs, as a model for human EoE. The pig combines high biological relevance based on their similarities to humans with a well-equipped immunological toolbox to study relevant disease-related immune responses. We believe that this large animal model will strongly impact research into EoE, and food allergy in general, and hasten development of new treatments and diagnostic procedures. Drawing on the NC State University College of Veterinary Medicine, the College of Sciences, and the School of Medicine at UNC we have assembled an interdisciplinary team with expertise in porcine immunology, the porcine gastrointestinal tract, and the clinical diagnosis and treatment of food allergy and EoE. Our preliminary, short term experiments show that we can indeed produce food allergic pigs (egg allergic) and we have observed the onset of inflammation in the esophagus. We are requesting funds to create a long-term state of chronic egg allergy to induce EoE in pigs, as it appears in humans. In addition, funding will be used to fully characterize the clinical and immunological features of disease. Once complete our model will be ready for scientists to test new treatments to slow or reverse disease or develop new diagnostic tests for early detection of EoE and food allergy.

食物过敏是一个日益严重的健康问题，对儿童和成人都有影响。尽管日益 食物过敏对人类健康和美国经济的影响（仅儿童就有250亿美元）和广泛的研究 尽管我们付出了巨大的努力，但仍然没有治愈食物过敏的方法。食物过敏的毁灭性症状之一是 被称为嗜酸性食管炎（EoE），其中对食物的反应导致严重的炎症， 食道（咽喉）。肿胀是痛苦的，并阻止固体食物的摄入。任何年龄的儿童和成人 年龄可能会发生EOE;儿童可能无法茁壮成长，青少年和成人的EOE可能会进展到食道 导致吞咽困难和食物嵌塞的狭窄。该提案要求提供资金， 翻译，大型动物模型的EoE。我们建议使用年轻的，食物过敏的猪，作为人类的模型， EoE。猪将基于与人类的相似性的高生物相关性与设备齐全的 免疫学工具箱，以研究相关疾病相关的免疫反应。我们相信这种大型动物 模型将强烈影响EoE和一般食物过敏的研究，并加速新的 治疗和诊断程序。借鉴北卡罗来纳州立大学兽医学院的经验， 科学学院，和医学院在威斯康星州，我们已经组装了一个跨学科的团队， 在猪免疫学、猪胃肠道以及猪腹泻的临床诊断和治疗方面的专业知识 食物过敏和EoE。我们初步的短期实验表明，我们确实可以产生食物过敏， 猪（鸡蛋过敏），我们已经观察到食道炎症的发作。我们正在申请资金 在猪中造成长期的慢性鸡蛋过敏状态，以诱导EoE，就像在人类中出现的那样。此外，本发明还提供了一种方法， 资金将用于充分确定疾病的临床和免疫学特征。一旦完成我们的 该模型将为科学家们测试新的治疗方法以减缓或逆转疾病或开发新的诊断方法做好准备。 早期检测EoE和食物过敏的测试。