整合的气道上皮信号网络将过敏原驱动的炎症与哮喘患者气道重塑联系起来
Integrated airway epithelial signaling networks linking allergen-driven inflammation to airway remodeling in asthma.
摘要(中文译文)
哮喘是一种慢性炎症性气道疾病，以持续性免疫激活、气道高反应性和进行性结构重塑为特征。气道上皮作为吸入性过敏原的主要感受器，通过释放警报素和趋化因子主动协调固有免疫和适应性免疫应答，同时通过上皮-间质转化和促纤维化介质的产生直接驱动结构改变。在过敏原（以屋尘螨为例）刺激下，气道上皮细胞激活一个整合的信号通路网络，包括表皮生长因子受体、丝裂原活化蛋白激酶、PI3K/蛋白激酶B、核因子κB（NF-κB）、Janus激酶/信号转导与转录激活因子（STAT）以及转化生长因子-β/SMAD通路，这些通路汇聚于关键转录因子，包括NF-κB/RelA、AP-1、STAT6、SMAD2/3和CCAAT/增强子结合蛋白β，协同诱导急性炎症因子的产生，包括警报素（胸腺基质淋巴细胞生成素（TSLP）、白细胞介素（IL）-33、IL-25）和趋化因子（C-C基序趋化因子配体20、C-X-C基序趋化因子配体8），以及慢性细胞重塑，包括杯状细胞增生、上皮下纤维化和平滑肌扩张。本综述以网络为中心全面整合了上述机制，特别关注哮喘内型异质性的分子基础、病毒性急性加重的放大作用、上皮炎症程序的表观遗传调控以及糖皮质激素抵抗的信号基础。此外，我们将嗜酸性粒细胞型、中性粒细胞型和混合型哮喘内型表型异质性的机制基础映射到特定的网络构型上，并讨论了涵盖已批准生物制剂、激酶抑制剂、屏障修复策略和联合方案的治疗意义。
Abstract
Asthma is a chronic inflammatory airway disease characterized by persistent immune activation, airway hyperresponsiveness, and progressive structural remodeling. The airway epithelium functions as the primary sensor of inhaled allergens and actively orchestrates both innate and adaptive immune responses through alarmin and chemokine release, while directly driving structural changes via epithelial-mesenchymal transition and profibrotic mediator production. Upon allergen challenge, exemplified by house dust mite, airway epithelial cells activate an integrated network of signaling pathways, including epidermal growth factor receptor, mitogen-activated protein kinase, PI3K/protein kinase B, nuclear factor kappa B (NF-κB), Janus kinase/signal transducer and activator of transcription (STAT), and transforming growth factor-β/SMAD, which converge on key transcription factors, including NF-κB/RelA, AP-1, STAT6, SMAD2/3, and CCAAT/enhancer-binding protein beta, to coordinately induce the production of acute inflammatory factors, including alarmins (thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, IL-25), and chemokines (C-C motif chemokine ligand 20, C-X-C motif chemokine ligand 8), as well as chronic cellular remodeling, including goblet cell hyperplasia, subepithelial fibrosis, and smooth muscle expansion. This review provides a comprehensive, network-centered synthesis of these mechanisms, with a particular focus on the molecular basis of asthma endotype heterogeneity, amplifying role of viral exacerbations, epigenetic regulation of epithelial inflammatory programs, and signaling basis of corticosteroid resistance. Further, we map the mechanistic basis of the phenotypic heterogeneity across eosinophilic, neutrophilic, and mixed asthma endotypes onto specific network configurations and then discuss therapeutic implications spanning approved biologics, kinase inhibitors, barrier-restoration strategies, and combinatorial approaches.
如何引用
AMA
Shin-Young Park. Integrated airway epithelial signaling networks linking allergen-driven inflammation to airway remodeling in asthma.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1884158.
APA
Shin-Young Park (2026). Integrated airway epithelial signaling networks linking allergen-driven inflammation to airway remodeling in asthma.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1884158
GB/T 7714
Shin-Young Park. Integrated airway epithelial signaling networks linking allergen-driven inflammation to airway remodeling in asthma.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1884158.
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