Neuromedin U induces airway goblet cell hypersecretion through eosinophil-derived interleukin-1α in allergic rhinitis

Title : Neuromedin U induces airway goblet cell hypersecretion through eosinophil-derived interleukin-1α in allergic rhinitis

Abstract:

Background: Neuropeptide neuromedin U (NMU) is elevated in allergic rhinitis (AR) and has been linked to eosinophil activation, but its role in goblet cell (GC) secretion during AR remains unclear. This study aimed to investigate whether NMU induces GC hypersecretion.

Methods: Nasal mucosal tissue samples were collected from healthy controls, AR patients, and those with non-allergic rhinitis with eosinophilia syndrome (NARES). The correlation between NMU expression and eosinophil peroxidase and MUC5AC was assessed. In vivo, eosinophil proportions in nasal and bronchoalveolar lavage fluids were quantified by flow cytometry, and GC numbers were measured using Alcian blue-periodic acid Schiff staining. Sensory nerve ablation in AR models was performed to assess mucus expression. A co-culture model of eosinophils and airway epithelial cells was used to examine MUC5AC and MUC5B secretion. After NMU induction in eosinophils, transcriptome sequencing was performed, and CellChat was used to analyze intercellular communication.

Results: NMU expression was higher in NARES and AR samples than in controls, correlating with an increased GC proportion in the inferior turbinate. In vivo, NMU stimulation increased eosinophil and GC proportions, while NMU inhibition attenuated these effects. Sensory nerve ablation reduced mucin and Nmu mRNA levels in nasal mucosa. In vitro, NMU increased MUC5AC and MUC5B secretion in co-cultured eosinophils and airway epithelial cells, but not in epithelial cells only. Transcriptomic analysis and CellChat revealed eosinophil-derived-IL-1α and IL-1R modulation on GCs, contributing to GC hypersecretion.

Conclusions: NMU increased MUC5AC secretion from GC through the activation of eosinophil-induced IL-1α. Trigeminal nerve ablation affected NMU expression and MUC5AC hypersecretion, highlighting a neuroimmune axis in AR pathogenesis.

Keywords: Allergic Rhinitis, Neuroimmune, Eosinophil, Goblet Cell Hypersecretion, Mucin, Neuromedin U

Biography:

Prof. Changqing Zhao received his Ph.D. from Xiangya School of Medicine, Hunan Medical University in 1995. As a leading expert in otorhinolaryngology, he serves as a Ph.D. supervisor, NSFC grant review expert, and former National Committee member of the Chinese Society of Otorhinolaryngology-Head and Neck Surgery. He pioneered the concept of the “nose-brain axis” to elucidate neuroimmune mechanisms in upper airway hyperresponsiveness, gaining international recognition. His work includes 300+ publications, with 46 high-impact SCI papers (e.g., JACI, Allergy), and two translated medical monographs (1 million words). He continues to shape therapeutic strategies for allergic respiratory diseases through translational neuroimmunology research.