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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结