Epithelial control of responses to allergen challenge and viral exacerbation

上皮细胞对过敏原挑战和病毒恶化反应的控制

• 批准号: 9315099
• 负责人: Steven F Ziegler
• 金额: $ 159.11万
• 依托单位: BENAROYA RESEARCH INST AT VIRGINIA MASON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9315099
• 关键词: Acute; Adhesions; Adrenal Cortex Hormones; Adult; Affect; Agonist; Air; Allergens; Allergic; Antigens; Asthma; Breathing; Cell Culture Techniques; Cell Differentiation process; Cells; Child; Childhood; Chronic; Chronic lung disease; Coculture Techniques; Cytoskeleton; Deposition; Development; Dictyoptera; Disease; Epithelial; Epithelial Cells; Epithelium; Extracellular Matrix; Extrinsic asthma; Fibroblasts; Frequencies; Functional disorder; Future; Goals; Hospitalization; Human; Hyaluronan; Immune; In Vitro; Individual; Infection; Infiltration; Inflammatory; Innate Immune Response; Interferons; Leukocytes; Link; Liquid substance; Lower Respiratory Tract Infection; Lung; Lymphoid; Mind; Minority Groups; Modeling; Morbidity - disease rate; Pathway interactions; Physicians; Play; Production; Pyroglyphidae; Recruitment Activity; Regulation; Respiratory physiology; Respiratory syncytial virus; Rhinovirus; Role; Schools; Severities; Structure; System; T cell response; T memory cell; T-Lymphocyte; Testing; Viral; Viral Respiratory Tract Infection; Virus; Virus Diseases; Visit; Work; adaptive immune response; airborne allergen; airway epithelium; airway hyperresponsiveness; airway inflammation; airway remodeling; asthmatic; asthmatic airway; chemokine; cytokine; design; disorder control; in vivo Model; insight; leukocyte activation; macrophage; mast cell; monocyte; mouse model; new therapeutic target; prevent; programs; respiratory infection virus; respiratory virus; response; standard of care; symptomatic improvement; treatment strategy; versican

Project Summary It is well known that infection by respiratory viruses (e.g., RSV or RV) can exacerbate responses in individuals who are allergic asthmatics. It is our hypothesis that the airway epithelium is the central coordinator of responses to respiratory virus infection, as well as to allergens. Intrinsic differences in airway epithelial cells (AEC) in healthy and asthmatic individuals play an important role in this exacerbated response. AECs from asthmatics respond in a different manner to infection than AECs from healthy subjects. These differences are manifested during infection in several ways, including changes in the expression and deposition of extra cellular matrix components and qualitative and quantitative differences in the expression of cytokines and chemokines. This altered response in asthmatic AEC leads to changes in both innate and adaptive responses during infection, with increased infiltration of the airways with leukocytes. The primary goal of this Program is to identify and characterize these changes in asthmatic AECs, and determine their effects on the innate and adaptive immune response. With this goal in mind, we will (1) Determine the role of the epithelium in regulating ECM and leukocyte adhesion in viral-triggered asthma; (2) Determine the regulation of the Innate Immune response by the epithelium in asthma; (3) Determine the role of the epithelium in regulating T cell responses in asthma.

项目概要 众所周知，呼吸道病毒（例如 RSV 或 RV）感染会加剧个体反应 谁是过敏性哮喘患者。我们的假设是，气道上皮是气道上皮细胞的中央协调者。 对呼吸道病毒感染以及过敏原的反应。气道上皮细胞的内在差异 （AEC）在健康和哮喘个体中在这种加剧的反应中发挥着重要作用。 AEC 来自 哮喘患者对感染的反应与健康受试者的 AEC 不同。这些差异是 在感染过程中以多​​种方式表现出来，包括额外的表达和沉积的变化 细胞基质成分以及细胞因子和细胞因子表达的定性和定量差异 趋化因子。哮喘 AEC 反应的这种改变导致先天反应和适应性反应的变化 感染期间，白细胞对气道的浸润增加。该计划的主要目标是 识别和描述哮喘 AEC 的这些变化，并确定它们对先天和 适应性免疫反应。考虑到这一目标，我们将 (1) 确定上皮细胞在 调节病毒引发的哮喘中的 ECM 和白细胞粘附； (2) 确定监管规则 哮喘中上皮细胞的先天免疫反应； (3) 确定上皮细胞的作用 调节哮喘中的 T 细胞反应。