Project 2. Basal Cell Dysplasia in Type 2 Immunopathology

项目2摘要/摘要 基底上皮细胞是形成所有分化上皮细胞亚群的干细胞样祖细胞。 除了它们的祖细胞功能外，它们还能产生包括白介素33(IL-33)在内的促炎分子。 33)和胸腺间质淋巴生成素(TSLP)，与2型(T2)炎症的病理生物学有关 湿疹、食物过敏、嗜酸性食管炎、哮喘和鼻息肉等疾病。我们的团队 最近报道慢性鼻窦炎鼻息肉病(CRSwNP)患者的基底细胞 发育不良，不能分化为正常的呼吸道上皮细胞，并上调生成能力 促炎分子。这些异常与异常的代谢程序有关。目标是 这项研究的计划是：1)确定基础细胞代谢如何调节它们的干细胞和促炎作用 功能，2)确定不同疾病患者鼻腔组织的基础细胞代谢如何改变 慢性鼻窦炎的类型，以及3)确定治疗抑制IL-4Rα是否会恢复 严重CRSwNP亚型阿司匹林-阿司匹林患者基底细胞的代谢、转录和表观遗传学变化 加重了呼吸道疾病。

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.