Accumulation of long-chain unsaturated fatty acids in the airway inflammatory microenvironment drives eosinophil etosis and corticosteroid resistance

作者：Yurong Bai, Pengda Fang, Shasha Li, Zhe Xiao, Wenyi Chen, Wenlong Li, Xinyue Wang, Jingyuan Chen, Yue Li, Junhai Chen, Weiqiang Huang, Xin Luo, Shigeharu Ueki, Deyu Fang, Qintai Yang, Yana Zhang · 发表于：Cell Communication and Signaling · 年份：2025 · DOI：10.1186/s12964-025-02217-9 · 被引用次数：5 · 研究领域：Sinusitis and nasal conditions、Asthma and respiratory diseases、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

BACKGROUND: Eosinophilic inflammation is a feature of chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with eosinophilic CRSwNP (ENP) tend to be refractory and prone to recurrence. Although there is increasing evidence linking lipid metabolic irregularities to eosinophilia, the particular lipid responsible for promoting eosinophilic inflammation and the precise molecular mechanisms involved remain unclear. METHODS: Lipidomic atlas and metabolic pathway enrichment were identified by liquid chromatography-tandem mass spectrometry and RNA sequencing, respectively. Eosinophil extracellular trap cell death (EETosis) was detected by immunofluorescence microscopy and transmission electron microscopy. Functional analyses were performed on purified eosinophils. RESULTS: The unbiased lipidomic atlas identified a specific accumulation in long-chain fatty acids (LCFAs) in ENP. Consistently, RNA-seq analysis confirmed the enrichment in long-chain unsaturated fatty acid metabolism pathway in ENP. In this lipid-rich airway inflammatory environment, EETosis including ETotic eosinophils, EETs release and Charcot-Leyden crystals (CLCs) generation was enhanced in ENP, and associated with disease severity. Further, we found that both saturated and unsaturated LCFAs, such as arachidonic acid, are critical fuel sources to trigger eosinophil activation and filamentous DNA release, whereas only arachidonic acid could induce crystalline Galectin10 (CLCs). Mechanistically, arachidonic acid ...