炎症诱导的CFTR表达性气道离子细胞在非酸性喘中的损失
Ling Chen1,2, Gabriela A Hoefel1,2, Prabuddha S Pathinayake2,3
1School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia.
非酸性喘包括囊性纤维化转膜导电性调节器 (CFTR) 功能减少和较少的CFTR表达性离子细胞. 这表明这种严重喘亚型的潜在新治疗标.
科学领域:
- 呼吸系统医学 呼吸系统医学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 严重的喘是异质的,通过气道透被分为异质性喘 (高2型) 或非异质性喘亚型.
- 非酸性喘包括酸性胞和中性胞类型,通常具有有限的治疗选择和对生物药物的反应不佳.
- 囊性纤维化跨膜导电调节器 (CFTR) 失调与呼吸系统疾病有关,使其成为潜在的治疗标.
研究的目的:
- 为了研究CFTR在非酸性喘中的作用.
- 为了确定CFTR功能和离子细胞分化是否在非酸性喘中发生变化.
主要方法:
- 来自患者和健康捐赠者的人类支气管上皮细胞 (hBEC) 在空气-液体界面培养.
- 单细胞RNA测序 (scRNAseq) 确定了上皮细胞亚型和转录特征.
- 使用乌辛室评估离子运输;在人类细胞和小鼠喘模型中量化离子细胞的丰度.
主要成果:
- 来自非酸性喘患者的hBEC显示CFTR功能降低和离子细胞分化受损.
- 在中性喘的小鼠模型的呼吸道中,离子细胞减少了,但不是异性喘.
- 模仿中性友性喘的炎症性细胞因子降低了健康供体hBECs中的离子细胞数量.
结论:
- 呼吸道细胞中CFTR表达性离子细胞的减少可能是非酸性喘发病的关键特征.
- 炎症引起的离子细胞损失代表了非酸性喘的潜在新疗法标.
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