The airway surface liquid (ASL) plays a crucial role in lung defense mechanisms, and its composition and volume are regulated by the airway epithelium. The cystic fibrosis transmembrane conductance regulator (CFTR) is abundantly expressed in a rare airway epithelial cell type called an ionocyte. Recently, we demonstrated that ionocytes can increase liquid absorption through apical CFTR and basolateral barttin/chloride channels, while airway secretory cells mediate liquid secretion through apical CFTR channels and basolateral NKCC1 transporters. Th2-driven (IL-4/IL-13) airway diseases, such as asthma, cause goblet cell metaplasia, accompanied by increased mucus production and airway secretions. In this study, we investigate the effect of IL-13 on chloride and liquid transport performed by ionocytes. IL-13 treatment of human airway epithelia was associated with reduced epithelial liquid absorption rates and increased ASL volume. Additionally, IL-13 treatment reduced the abundance of CFTR-positive ionocytes and increased the abundance of CFTR-positive secretory cells. Increasing ionocyte abundance attenuated liquid secretion caused by IL-13. Finally, CFTR-positive ionocytes were less common in asthma and chronic obstructive pulmonary disease and were associated with airflow obstruction. Our findings suggest that loss of CFTR in ionocytes contributes to the liquid secretion observed in IL-13–mediated airway diseases.

中文翻译：

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IL-13 诱导离子细胞中 CFTR 的丢失并减少气道上皮液的吸收


气道表面液 （ASL） 在肺防御机制中起着至关重要的作用，其组成和体积受气道上皮细胞的调节。囊性纤维化跨膜电导调节因子 （CFTR） 在一种称为离子细胞的罕见气道上皮细胞类型中大量表达。最近，我们证明离子细胞可以通过顶端 CFTR 和基底外侧 barttin/chloride 通道增加液体吸收，而气道分泌细胞通过顶端 CFTR 通道和基底外侧 NKCC1 转运蛋白介导液体分泌。Th2 驱动的 （IL-4/IL-13） 气道疾病，例如哮喘，会导致杯状细胞化生，并伴有粘液产生和气道分泌物增加。在这项研究中，我们研究了 IL-13 对离子细胞进行的氯化物和液体运输的影响。IL-13 治疗人气道上皮细胞与上皮液体吸收率降低和 ASL 体积增加相关。此外，IL-13 处理降低了 CFTR 阳性离子细胞的丰度，并增加了 CFTR 阳性分泌细胞的丰度。离子细胞丰度的增加减弱了 IL-13 引起的液体分泌。最后，CFTR 阳性离子细胞在哮喘和慢性阻塞性肺病中不太常见，并且与气流阻塞有关。我们的研究结果表明，离子细胞中 CFTR 的丢失有助于在 IL-13 介导的气道疾病中观察到的液体分泌。