Project 2. Basal Cell Dysplasia in Type 2 Immunopathology

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。

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.