Alleviation of Chitin- and Ovalbumin-Induced Steroid-Resistant Eosinophilic Airway Inflammation Associated with NLRP3 Axis Inhibition in a Mouse Model.

BACKGROUND: Steroid resistance complicates asthma management in some patients. However, its mechanisms remain unclear. In our previous study, we developed a novel mouse model using inhaled chitin-a pathogen-associated molecular pattern-which, when combined with ovalbumin (OVA), induces steroid-resistant airway inflammation and airway hyperresponsiveness. This study aimed to investigate the specific intrapulmonary lymphocyte populations implicated in the pathogenesis of chitin-induced steroid-resistant asthma and evaluate the therapeutic potential of NLRP3 inflammasome inhibition in reversing this resistance. METHODS: BALB/c mice were intranasally challenged with OVA alone or OVA combined with chitin, with or without dexamethasone (DEX). Lung cells were harvested 24 h after the final challenge and analyzed using flow cytometry. RESULTS: Co-stimulation with OVA and chitin significantly increased the total number of lung cells, eosinophils, IL-17-producing Th cells, ILC2s, invariant natural killer T (iNKT) cells, and mucosal-associated invariant T (MAIT) cells. Although DEX effectively suppressed these immune responses induced by OVA alone, it could not inhibit responses induced by OVA/chitin. Notably, administering an NLRP3 inflammasome inhibitor restored steroid sensitivity, reducing eosinophilic inflammation and dampening the number of Th17, ILC2s, iNKT, and MAIT cells. CONCLUSION: Our findings suggest that the NLRP3 axis may play a role in chitin-induced steroid-resistant eosinophilic airway inflammation. Targeting this axis, together with corticosteroids, could be a potential therapeutic strategy.