Solitary chemosensory / tuft cells in lung regeneration and inflammation

肺再生和炎症中的孤立化学感应/簇细胞

基本信息

批准号：
10171904
负责人：
Andrew Vaughan
金额：
$ 39.93万
依托单位：
UNIVERSITY OF PENNSYLVANIA
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：
2020-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10171904
关键词：
Ablation Acetylcholine Address Adult Affect Asthma Attenuated Blood Body Weight decreased Brush Cell Cell Differentiation process Cell Lineage Cell physiology Cells Childhood Asthma Chronic Chronic Disease Chronic Obstructive Airway Disease Chronic lung disease Cicatrix Cre driver Cytokeratin Data Development Diphtheria Toxin Disease Distal Effector Cell Eicosanoids Epithelial Epithelial Cells Etiology Exhibits Exposure to Fibrosis Frequencies Gases Genes Genetic Goblet Cells Immunity Individual Infection Inflammation Inflammatory Influenza Influenza A Virus, H1N1 Subtype Injury Interleukin-13 Interstitial Lung Diseases Intestines Intraepithelial Neoplasia Link Lung Lung Inflammation Lung diseases Lymphoid Measures Mediating Metaplastic Cell Modeling Mus Natural regeneration Nippostrongylus Organoids Output Paracrine Communication Parasites Pathogen detection Pathologic Pathology Pathway interactions Phenotype Predisposition Pulmonary Pathology Pyroglyphidae Resolution Risk Factors Signal Transduction Testing Time Tissues Viral Viral Respiratory Tract Infection airway hyperresponsiveness asthmatic base chronic inflammatory lung disease cytokine diphtheria toxin receptor eosinophil epithelial repair epithelial stem cell helminth infection immunopathology influenza infection injured lung development lung injury lung regeneration mucosal site neutralizing antibody overexpression pathogen preservation prevent pulmonary function repaired respiratory pathogen response small molecule surfactant therapeutic target tissue regeneration tissue repair tool transcription factor

项目摘要

Project Summary / Abstract Respiratory viral infections represent a major risk factor for the development of asthma. Moreover, severe influenza injury can result in ineffective repair and persistent loss of pulmonary function. The enduring changes caused by viral-induced lung injury that might explain chronic disease are not understood. We recently identified ectopic tuft / solitary chemosensory cells (SCCs) arising in the distal lung after H1N1 influenza infection. Since SCCs are increasingly recognized as critical orchestrators of both inflammation and epithelial tissue regeneration and remodeling, we posit that they are a likely driver of chronic lung pathology. This proposal will address the central hypothesis that inactivation / ablation of ectopic SCCs will promote the resolution of dysplastic remodeling and reduce chronic Th2-biased inflammatory disease, but may also increase susceptibility to pathogens controlled by Th2 responses following influenza infection. The major aims to address this hypothesis are to 1) ascertain the effects of SCC presence and specific SCC-derived signals on epithelial progenitor cells (fate and proliferation) during repair, and 2) determine whether the development of SCCs impacts Th2-mediated inflammatory disease (asthma) or parasitic protection. Completion of this project will validate SCCs as important drivers of pulmonary disease and will also facilitate identification of specific SCC effector pathways that could allow for preservation of host-protective benefits while attenuating their contribution to pathology.

项目概要/摘要呼吸道病毒感染是哮喘发生的主要危险因素。此外，严重的流感损伤会导致修复无效和持续丧失肺功能。病毒引起的肺损伤引起的持久变化可能无法解释慢性疾病。我们最近发现了异位簇/ H1N1 流感后远端肺中出现孤立化学感应细胞 (SCC) 感染。由于 SCC 越来越被认为是两者的关键协调者炎症和上皮组织再生和重塑，我们认为它们是慢性肺部病理的可能驱动因素。该提案将针对中央假设异位 SCC 的灭活/消融将促进消退发育不良重塑并减少慢性 Th2 偏向性炎症性疾病，但也可能增加对 Th2 反应控制的病原体的易感性感染流感后。解决这一假设的主要目的是：1) 确定 SCC 的存在和特定 SCC 衍生信号对上皮细胞的影响修复期间的祖细胞（命运和增殖），以及 2) 确定是否 SCC 的发展会影响 Th2 介导的炎症性疾病（哮喘）或寄生保护。该项目的完成将验证 SCC 作为重要驱动因素肺部疾病，也将有助于识别特定的 SCC 效应子可以在减弱宿主保护益处的同时保留宿主保护益处的途径他们对病理学的贡献。