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Epithelial regulation of ECM and leukocyte adhesion in viral-triggered asthma

病毒引发的哮喘中 ECM 和白细胞粘附的上皮调节

基本信息

批准号：
10160630
负责人：
Steven F Ziegler
金额：
$ 8.58万
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：
2020
资助国家：
美国
起止时间：
2020-05-14 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10160630
关键词：
2019-nCoV Address Adhesions Administrative Supplement Adult Affect Age Age-Years Air Allergens Allergic Asthma Biological Models COVID-19 Case Fatality Rates Cell Culture Techniques Cell Death Cells Child Coronavirus Cytoskeleton Data Deposition Development Diabetes Mellitus Disease Elderly Epithelial Epithelial Cells Epithelium Exhibits Extracellular Matrix Failure Fatality rate Genes Genetic Genetic Screening Goals Grant Heterogeneity Hypertension Immune Immune response Incidence Individual Infection Infiltration Inflammatory Innate Immune Response Integrin alphaV Interferon Type I Interferons Leukocytes Liquid substance Lung Mind Mutagenesis Obesity Older Population Parents Pathogenicity Pathway interactions Patients Play Pneumonia Positioning Attribute Predisposition Primary Infection Process Production Reagent Regulation Resistance Resources Respiratory Failure Respiratory Syncytial Virus Infections Role SARS coronavirus Sampling Severities Severity of illness Social Distance Symptoms T cell response T-Lymphocyte Techniques Testing Therapeutic Tissues Viral Virus Virus Diseases Virus Replication Virus Shedding Virus-Cell Membrane Interaction Work adaptive immune response age group airway epithelium asthmatic asthmatic airway chemokine cohort comorbidity cytokine high risk human coronavirus improved infection rate lung injury monocyte novel therapeutics pandemic disease parent grant prevent programs recruit respiratory infection virus respiratory virus response therapeutic target tissue injury virus host interaction

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.

项目摘要众所周知，呼吸道病毒感染（例如，RSV或RV）可加重个体的反应过敏性哮喘患者我们假设气道上皮细胞是呼吸系统的中枢协调者。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起重要作用。AECs来自哮喘患者对感染的反应方式与健康受试者的AEC不同。这些差异是在感染过程中表现在几个方面，包括表达和沉积的变化，额外的细胞基质成分和细胞因子表达的定性和定量差异，趋化因子哮喘AEC中这种改变的反应导致先天性和适应性反应的变化在感染期间，随着白细胞对气道的浸润增加。该计划的主要目标是识别和表征哮喘AEC中的这些变化，并确定它们对先天性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触发哮喘中的ECM和白细胞粘附;（2）确定病毒触发哮喘中ECM和白细胞粘附的调节。哮喘中上皮细胞的天然免疫反应;（3）确定上皮细胞在哮喘中的作用，调节哮喘中的T细胞反应。