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Project 2. Basal Cell Dysplasia in Type 2 Immunopathology

项目 2. 2 型免疫病理学中的基底细胞发育不良

基本信息

批准号：
10456245
负责人：
Nora Amanda Barrett
金额：
$ 37.57万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-15 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10456245
关键词：
Airway Disease Asthma Automobile Driving Basal Cell Biological Assay Bronchiectasis Cell Adhesion Molecules Cell Aging Cell Differentiation process Cell physiology Cellular Assay Cellular Metabolic Process Chromatin Structure Chronic Obstructive Pulmonary Disease Communities Data Development Dinoprostone Disease Dysplasia Eczema Eosinophilic Esophagitis Epigenetic Process Epithelial Epithelial Cells FDA approved FRAP1 gene Failure Food Hypersensitivity Funding Galactosidase Generations Genes Genetic Transcription Goals Homeostasis Human Hypertrophy Immune Inflammatory Interleukin 4 Receptor Interleukin-13 Interleukin-4 Interleukins Interruption Maintenance Mediator of activation protein Metabolic Metabolic Pathway Metabolism Molecular Mus Nasal Polyps Nose Pathogenesis Pathway interactions Patients Polyps Population Recurrent disease Relapse Reporting Research Resources Role Signal Transduction Site TSLP gene Therapeutic Tissues Transcript airway epithelium airway inflammation aspirin-exacerbated respiratory disease chronic rhinosinusitis cytokine epithelial stem cell genetic signature genome wide association study immunopathology imprint long-term sequelae mouse model polyposis prevent progenitor programs respiratory response senescence stem stem cells stem-like cell transcriptomics wound healing

项目摘要

Project 2 Summary/Abstract Basal epithelial cells are the stem-like progenitor cells that give rise to all differentiated epithelial cell subsets. In addition to their progenitor function, they produce pro-inflammatory molecules including interleukin-33 (IL- 33) and thymic stromal lymphopoietin (TSLP), implicated in the pathobiology of type 2 (T2) inflammatory diseases such as eczema, food allergy, eosinophilic esophagitis, asthma, and nasal polyposis. Our group recently reported that basal cells from patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) are dysplastic, fail to differentiate into normal respiratory epithelial cells, and upregulate the capacity to generate proinflammatory molecules. These abnormalities are associated with an aberrant metabolic program. The goal of this research plan is to: 1) define how basal cell metabolism regulates their stem and proinflammatory functions, 2) determine how basal cell metabolism is altered in the sinonasal tissue of patients with different types of chronic rhinosinusitis, and 3) determine whether therapeutic inhibition of IL-4Rα will restore the metabolic, transcriptional, and epigenetic changes seen in basal cells in a severe CRSwNP subtype, aspirin- exacerbated respiratory disease.

项目2概要/摘要基底上皮细胞是产生所有分化的上皮细胞亚群的干细胞样祖细胞。除了它们的祖细胞功能，它们还产生促炎分子，包括白细胞介素-33（IL-10）。 33)和胸腺基质淋巴细胞生成素（TSLP），涉及2型（T2）炎性湿疹、食物过敏、嗜酸性食管炎、哮喘和鼻息肉病等疾病。我们集团最近报道，慢性鼻窦炎伴鼻息肉病（CRSwNP）患者的基底细胞，不典型增生，不能分化成正常的呼吸道上皮细胞，并上调生成促炎分子这些异常与代谢程序异常有关。目标这项研究计划的主要目的是：1）确定基底细胞代谢如何调节其干细胞和促炎细胞因子功能，2）确定基底细胞代谢在不同疾病患者的鼻窦组织中是如何改变的慢性鼻窦炎的类型，和3）确定治疗性抑制IL-4 R α是否会恢复在严重CRSwNP亚型的基底细胞中观察到代谢、转录和表观遗传变化，阿司匹林- 呼吸道疾病加重。