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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：
10168800
负责人：
Steven F Ziegler
金额：
$ 92.44万
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/10168800
关键词：
2019-nCoV Acute Adhesions Adrenal Cortex Hormones Adult Affect Agonist Air Allergens Allergic Antigens Asthma COVID-19 Cell Culture Techniques Cell Differentiation process Cells Child Childhood Chronic Chronic lung disease Coculture Techniques Cytoskeleton Data Deposition Development Dictyoptera Disease Epithelial Epithelial Cells Epithelium Extracellular Matrix Extrinsic asthma Fibroblasts Frequencies Functional disorder Future Genes Goals Hospitalization Human Hyaluronan Immune In Vitro Individual Infection Infiltration Inflammatory Inhalation Innate Immune Response Interferons Leukocytes Link Liquid substance Lower Respiratory Tract Infection Lung Mind Minority Groups Modeling Morbidity - disease rate Pathway interactions Physicians Play Process Production Pyroglyphidae Regulation Resources Respiratory physiology Respiratory syncytial virus Rhinovirus Role Schools Severities System T cell response T memory cell T-Lymphocyte Testing Therapeutic Viral Viral Respiratory Tract Infection Virus Diseases Virus Replication Visit Work adaptive immune response airborne allergen airway epithelium airway hyperresponsiveness airway inflammation airway remodeling asthma exacerbation asthmatic asthmatic airway chemokine cytokine disorder control in vivo Model leukocyte activation lymphoid structures macrophage mast cell monocyte mouse model prevent programs recruit 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.

项目摘要众所周知，感染呼吸道病毒(如呼吸道合胞病毒或轮状病毒)会加剧个体的反应他们都是过敏性哮喘患者。我们的假设是，呼吸道上皮是对呼吸道病毒感染和过敏原的反应。呼吸道上皮细胞的内在差异健康人和哮喘患者的血管内皮细胞(AEC)在这种加重的反应中起着重要作用。AECS发件人哮喘患者对感染的反应方式与健康人的血管内皮细胞不同。这些区别是在感染过程中表现为几种方式，包括Extra的表达和沉积的变化细胞基质成分与细胞因子和细胞因子表达的质与量差异趋化因子。哮喘AEC中这种改变的反应导致先天反应和适应性反应的改变在感染期间，随着白细胞在呼吸道的渗透增加。该计划的主要目标是鉴定和表征哮喘AECs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)确定上皮在调节病毒触发的哮喘中的ECM和白细胞黏附；(2)确定哮喘中上皮细胞的先天免疫反应；(3)上皮细胞在哮喘发病中的作用调节哮喘患者的T细胞反应。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Apoptotic Cell-Directed Resolution of Lung Inflammation Requires Myeloid αv Integrin-Mediated Induction of Regulatory T Lymphocytes.

肺部炎症的凋亡细胞定向解决需要骨髓αv整合素介导的调节性T淋巴细胞的诱导。

DOI：
10.1016/j.ajpath.2020.02.010
发表时间：
2020
期刊：
The American journal of pathology
影响因子：
0
作者：
Zhang,Ailiang;Lacy-Hulbert,Adam;Anderton,Stephen;Haslett,Christopher;Savill,John
通讯作者：
Savill,John

GM-CSF produced by the airway epithelium is required for sensitization to cockroach allergen.