Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado, USA.
JCI Insight. 2022 Jul 8;7(13):e159832. doi: 10.1172/jci.insight.159832.
Chronic type 2 (T2) inflammatory diseases of the respiratory tract are characterized by mucus overproduction and disordered mucociliary function, which are largely attributed to the effects of IL-13 on common epithelial cell types (mucus secretory and ciliated cells). The role of rare cells in airway T2 inflammation is less clear, though tuft cells have been shown to be critical in the initiation of T2 immunity in the intestine. Using bulk and single-cell RNA sequencing of airway epithelium and mouse modeling, we found that IL-13 expanded and programmed airway tuft cells toward eicosanoid metabolism and that tuft cell deficiency led to a reduction in airway prostaglandin E2 (PGE2) concentration. Allergic airway epithelia bore a signature of PGE2 activation, and PGE2 activation led to cystic fibrosis transmembrane receptor-dependent ion and fluid secretion and accelerated mucociliary transport. These data reveal a role for tuft cells in regulating epithelial mucociliary function in the allergic airway.
慢性 2 型（T2）呼吸道炎症性疾病的特征是粘液过度产生和粘液纤毛功能紊乱，这在很大程度上归因于 IL-13 对常见上皮细胞类型（粘液分泌细胞和纤毛细胞）的影响。罕见细胞在气道 T2 炎症中的作用尚不清楚，尽管已经表明微绒毛发细胞在肠道 T2 免疫的启动中至关重要。通过对气道上皮细胞进行批量和单细胞 RNA 测序以及小鼠建模，我们发现 IL-13 扩增并将气道微绒毛发细胞编程为类二十烷酸代谢，而微绒毛发细胞缺陷会导致气道前列腺素 E2（PGE2）浓度降低。过敏性气道上皮细胞具有 PGE2 激活的特征，PGE2 激活导致囊性纤维化跨膜受体依赖性离子和液体分泌，并加速粘液纤毛转运。这些数据揭示了微绒毛发细胞在调节过敏性气道上皮粘液纤毛功能中的作用。
