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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.

性状（由申请方提供）：粘膜表面的上皮细胞是宿主抵抗外源性产物和病原体的第一道屏障。肠上皮细胞（IEC）因其在消化和选择性吸收摄入的食物分子中的作用而被广泛研究。IEC产生影响经典抗原呈递细胞和其他先天细胞分化的细胞因子，随后形成适应性免疫应答。这些细胞还表达多聚免疫球蛋白的受体，其允许多聚伊加穿过上皮转运并在管腔中分泌为分泌型伊加抗体。然而，IEC在过敏反应中的作用仍然知之甚少，并且仍然不清楚IEC中的特定信号传导途径如何影响胃肠道中的过敏致敏作用以及如何影响远处粘膜部位（如气道）的过敏反应。我们将解决的总体假设，在肠上皮细胞中选择的先天性信号传导途径的形状过敏原特异性抗体同种型反应，并促进伊加抗体，这可以防止发展，或减少过敏性炎症的程度在遥远的网站。使用遗传修饰的小鼠和选定的先天性信号传导途径的药物抑制剂，我们提出1）解决肠上皮细胞中非经典NF κ B B信号传导的激活如何影响肠上皮细胞中NF κ B的表达。 2）建立伊加和伊加+ B细胞对过敏性炎症的保护机制。