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。

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）

Phase 1 trial supports safety and mechanism of action of peptide immunotherapy for peanut allergy.

一期试验支持肽免疫疗法治疗花生过敏的安全性和作用机制。

DOI：
10.1111/all.15966
发表时间：
2023-12-19
期刊：
Allergy
影响因子：
12.4
作者：
A. Voskamp;Sug;hika Khosa;hika;Tracy Phan;Hannah A. DeBerg;Judy Bingham;M. Hew;William Smith;Jodie Abramovitch;Jennifer M Roll;Matthew Moyle;K. Nadeau;G. Lack;M. Larché;E. Wambre;Robyn E. O’Hehir;Pascal L. C. Hickey;S. Prickett
通讯作者：
S. Prickett

Apoptotic cells induce CD103 expression and immunoregulatory function in myeloid dendritic cell precursors through integrin αv and TGF-β activation.

凋亡细胞通过整合素αv 和TGF-β 激活诱导骨髓树突状细胞前体中的CD103 表达和免疫调节功能。

DOI：
发表时间：
2020
期刊：
影响因子：
3.7
作者：
Zhang, Ailiang;Paidassi, Helena;Lacy;Savill, John
通讯作者：
Savill, John

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

气道上皮产生的 GM-CSF 是对蟑螂过敏原敏感所必需的。

DOI：
发表时间：
2017-05
期刊：
影响因子：
8
作者：
Sheih, A;Parks, W C;Ziegler, S F
通讯作者：
Ziegler, S F

The atopic march: current insights into skin barrier dysfunction and epithelial cell-derived cytokines.

特应性游行：对皮肤屏障功能障碍和上皮细胞衍生细胞因子的最新见解。

DOI：
发表时间：
2017-07
期刊：
影响因子：
8.7
作者：
Han, Hongwei;Roan, Florence;Ziegler, Steven F
通讯作者：
Ziegler, Steven F

TSLP drives acute TH2-cell differentiation in lungs.

TSLP 驱动肺部 TH2 细胞急性分化。

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
Lai, Jen;Thompson, Lucas J;Ziegler, Steven F
通讯作者：
Ziegler, Steven F

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Steven F Ziegler其他文献

Diversity of group 1 innate lymphoid cells in human tissues.

人体组织中第 1 组先天淋巴细胞的多样性。

DOI：
发表时间：
2024
期刊：
Nature Immunology
影响因子：
30.5
作者：
N. Jaeger;A. U. Antonova;Daniel Kreisel;F. Roan;Erica Lantelme;Steven F Ziegler;M. Cella;Marco Colonna
通讯作者：
Marco Colonna