LPS-HDM-Induced Asthma Model: A Translational Platform for Neutrophilic Asthma and Glucocorticoid-Resistant Inflammation 2256839

Abstract

Abstract Introduction Asthma is a heterogeneous inflammatory airway disease characterized by complex immunopathogenesis. Up to 50% of patients present with a non-Th2-type inflammatory phenotype, characterized by neutrophilic inflammation and poor responsiveness to conventional glucocorticoids. This glucocorticoid-resistant phenotype represents a major unmet clinical need, yet current preclinical models do not capture its underlying mechanisms adequately. Methods To address this gap, we developed a murine model of neutrophilic asthma induced by the combined exposure to lipopolysaccharide (LPS) and house dust mite (HDM), and evaluation the immune cell population in the lung and bronchoalveolar Lavage fluid. Results This LPA-HDM model recapitulates the key hallmark features of non-TH2 asthma, including airway neutrophilia, macrophage infiltration, and airway remodeling. Importantly, the model demonstrates resistance to glucocorticoid (dexamethasone) treatment, mirroring the clinical phenotype of glucocorticoid-refractory asthma. Conclusion The LPS-HDM-induced asthma model provides a robust and reproducible preclinical platform for advancing the mechanistic understanding of neutrophilic asthma and accelerating the development of precision therapies for this challenging patient population. Funding Source n/a Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)