Regulation of the Innate Immune Response by the Epithelium in Asthma

哮喘中上皮细胞对先天免疫反应的调节

基本信息

批准号：
10202415
负责人：
TEAL S HALLSTRAND
金额：
$ 49.2万
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/10202415
关键词：
2019-nCoV Address Adhesions 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

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.

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。