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

• 批准号: 10627810
• 负责人: Andrew Vaughan
• 金额: $ 39.94万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 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/10627810
• 关键词: Ablation; Acetylcholine; Address; Adult; Affect; Airway Fibrosis; Alveolus; Asthma; Blood; Body Weight decreased; Brush Cell; Cell Differentiation process; Cell Lineage; Cell physiology; Cells; Childhood Asthma; Chronic; Chronic Disease; Chronic Obstructive Pulmonary Disease; Chronic lung disease; Cicatrix; Cre driver; Cytokeratin; Data; Development; Diphtheria Toxin; Disease; Distal; Effector Cell; Eicosanoids; Epithelial Cells; Epithelium; Etiology; Exhibits; Exposure to; 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 diseases; Lymphoid; Measures; Mediating; Metaplasia; Modeling; Mus; Natural regeneration; Nippostrongylus; Organoids; Output; Paracrine Communication; Parasites; Pathogen detection; Pathologic; Pathology; Pathway interactions; Phenotype; Predisposition; Proliferating; Pulmonary Inflammation; Pulmonary Pathology; Pyroglyphidae; Resolution; Risk Factors; Sensory; Signal Transduction; Testing; Time; Tissues; Viral; Viral Respiratory Tract Infection; Virus Diseases; airway hyperresponsiveness; asthmatic; 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 pathogen; lung regeneration; mucosal site; neutralizing antibody; overexpression; pathogen; preservation; prevent; pulmonary function; repaired; response; small molecule; surfactant; therapeutic target; tissue regeneration; tissue repair; tool; transcription factor

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。

项目成果

Unusual X chromosome inactivation maintenance in female alveolar type 2 cells is correlated with increased numbers of X-linked escape genes and sex-biased gene expression.

• DOI: 10.1016/j.stemcr.2022.12.005
• 发表时间: 2023-02-14
• 期刊: STEM CELL REPORTS
• 影响因子: 5.9
• 作者: Sierra, Isabel;Pyfrom, Sarah;Weiner, Aaron;Zhao, Gan;Driscoll, Amanda;Yu, Xiang;Gregory, Brian D.;Vaughan, Andrew E.;Anguera, Montserrat C.
• 通讯作者: Anguera, Montserrat C.

Basal-like Progenitor Cells: A Review of Dysplastic Alveolar Regeneration and Remodeling in Lung Repair.

基底样祖细胞：对肺修复中肺泡再生和重塑的综述。

• DOI: 10.1016/j.stemcr.2020.09.006
• 发表时间: 2020-11-10
• 期刊: Stem cell reports
• 影响因子: 5.9
• 作者: Fernanda de Mello Costa M;Weiner AI;Vaughan AE
• 通讯作者: Vaughan AE

An injury-induced tissue niche shaped by mesenchymal plasticity coordinates the regenerative and disease response in the lung.

由间充质可塑性形成的损伤诱导的组织生态位协调肺部的再生和疾病反应。

• DOI: 10.1101/2024.02.26.582147
• 发表时间: 2024
• 期刊: bioRxiv : the preprint server for biology
• 作者: Jones,DakotaL;Morley,MichaelP;Li,Xinyuan;Ying,Yun;Cardenas-Diaz,FabianL;Li,Shanru;Zhou,Su;Schaefer,SarahE;Chembazhi,UllasV;Nottingham,Ana;Lin,Susan;Cantu,Edward;Diamond,JoshuaM;Basil,MariaC;Vaughan,AndrewE;Morrisey,E
• 通讯作者: Morrisey,E