Regulation of mucosal IgA and allergic inflammation by intestinal epithelial cells

肠上皮细胞对粘膜IgA和过敏性炎症的调节

基本信息

批准号：
9095324
负责人：
Prosper N Boyaka
金额：
$ 34.48万
依托单位：
OHIO STATE UNIVERSITY
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：
2015-07-01 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9095324
关键词：
Address Affect Allergens Allergic Allergic Disease Allergic inflammation American Americas Antibodies Antigen-Presenting Cells Antigens Asthma Attenuated B-Lymphocytes Binding Cell Line Cell Shape Cells Country Development Digestion Distant Dose Eosinophilia Epithelial Cells Epithelium Equilibrium Event Exhibits Extrinsic asthma Food Food Hypersensitivity Foundations Gastrointestinal tract structure Grant Health Hypersensitivity IgE Immunoglobulin A Immunoglobulin Isotypes Incidence Inflammation Injection of therapeutic agent Integrins Interferon Type II Interleukin-13 Interleukin-17 Interleukin-4 Interleukin-5 Intestines Knowledge Lead Lung Inflammation Lymphocyte antigen CD50 Mediating Modeling Molecular Mucous Membrane Mucous body substance Mus Myeloid Cells Neutrophil Infiltration Nose Pathway interactions Persons Pharmaceutical Preparations Pharmacologic Substance Phenotype Play Polymeric Immunoglobulin Receptors Process Production Public Health Regulation Role Secretory Immunoglobulin A Shapes Signal Pathway Signal Transduction Site Surface Testing Th1 Cells Work absorption adaptive immunity airway hyperresponsiveness allergic airway inflammation allergic response anti-IgE antigen challenge cell type cost cytokine desensitization food allergen inhibitor/antagonist insight mucosal site novel therapeutic intervention pathogen polymeric IgA prevent protective effect receptor response stem

项目摘要

DESCRIPTION (provided by applicant): Epithelial cells lining mucosal surfaces represent the first barrier of the host against exogenous products and pathogens. Intestinal epithelial cells (IEC) have been extensively studied for their role in the digestion and selective absorption of ingested food molecules. IEC produce cytokines that influence the differentiation of classical antigen presenting and other innate cells and subsequently, shape adaptive immune responses. These cells also express the receptor for polymeric immunoglobulins, which allows the transport of polymeric IgA across the epithelium and their secretion as secretory IgA antibodies in the lumen. However, the role of IEC in allergic responses remains poorly understood and it remains unclear how specific signaling pathways in IEC affect allergic sensitization in the GI tract and impact allergic responses at distant mucosal sites such as the airways. We will address the overall hypothesis that selected innate signaling pathway in intestinal epithelial cells shape allergen-specific antibody isotype responses and promote IgA antibodies, which can prevent the development, or reduce the magnitude of allergic inflammation at distant sites. Using genetically modified mice and pharmaceutical inhibitors of the selected innate signaling pathway we propose to 1) address how activation of the non-canonical NFB signaling in intestinal epithelial cells regulate adaptive immune response during allergic sensitization; 2) Establish mechanisms of protection against allergic inflammation by IgA and IgA+ B cells.

描述（由适用提供）：上皮细胞衬里粘膜表面代表宿主对外源产物和病原体的第一个障碍。肠上皮细胞（IEC）在摄入食品分子的消化和选择性苦难中的作用已广泛研究。 IEC产生的细胞因子会影响经典抗原呈递和其他先天细胞的分化，然后形成适应性免疫调查。这些细胞还表达了聚合物免疫球蛋白的接收器，该接收器允许聚合物IgA在整个上皮及其分泌物中作为腔内秘书IgA抗体的分泌。但是，IEC在过敏反应中的作用仍然鲜为人知，尚不清楚IEC中特定的信号通路如何影响胃肠道的过敏敏感性并影响远处粘膜位点（如Airways）的过敏反应。我们将解决这样的总体假设：肠上皮细胞中选择的先天信号通路塑造过敏原特异性抗体同种型反应并促进IgA抗体，从而可以防止发育或减少可识别位点过敏感染的大小。使用所选先天信号通路的一般修饰的小鼠和药物抑制剂，我们建议1）解决肠上皮上上皮中非典型NFB信号的激活细胞在过敏敏感性期间调节适应性免疫响应； 2）建立IgA和IgA+ B细胞过敏注射的保护机制。