Development and translational validation of a novel mouse model for allergic rhinitis

Background: Approximately 30% of the North American population are affected by seasonal or perennial rhinitis. Allergens from cats are common triggers of allergic rhinitis. Importantly, cat allergic rhinitis (cat-AR) is a major risk factor for more severe allergic diseases, including asthma. Current therapies rarely achieve full symptom control and development of novel therapeutics is constrained by the lack of physiologically relevant preclinical models. Objective: Establishment of a clinically-informed mouse model of cat allergen exposure in humans. Methods: Controlled human exposure was performed using airborne natural cat dander (CD) in a validated environmental exposure facility. Nasal immune cells and IgE concentrations in serum and nasal samples were assessed. In mice, we established a 14-day intermittent intranasal sensitization and challenge protocol using the same CD allergens. Clinical signs in mice were objectively quantified using AI-based video detection. Cellular changes in the nose were assessed with level-specific, spatial resolution. Lastly, systemic sensitization was confirmed through serum IgE and intradermal ear challenge. Measurements and Main Results: Following CD exposure, cat-allergic participants displayed increased nasal symptoms and eosinophil influx. CD-sensitized mice recapitulated key clinical features, including increased nasal rubbing, elevated nasal immune cell infiltration, and systemic sensitization. Importantly, spatial investigation of the cellular changes revealed major changes in the turbinate and olfactory regions of the nose. Conclusions: This novel mouse model provides a translationally valuable platform for investigating local and systemic mechanisms of cat-AR. It will serve for mechanistic and therapeutic evaluations with the goal of improving clinical translation and therapeutic precision.