Humanizing chitinase activity variants in allergic airway disease 2375

Abstract Description Chitin, a natural polysaccharide found in environmental allergens and pathogens, is known to activate immune responses. However, the impact of impaired chitin clearance on chronic inflammation and allergic disease remains unclear. To investigate, we developed a mouse model (hChia) with a humanized AMCase variant exhibiting reduced chitinase activity, allowing us to study the effects of persistent chitin accumulation on airway immunity. At baseline, hChia mice demonstrated heightened CD4+ T cell activation, indicating a primed immune state. Upon IL-1β + IL-23 stimulation, T cell responses were significantly elevated in hChia, suggesting increased sensitivity to inflammatory cues. Following house dust mite (HDM) exposure, hChia mice exhibited stronger eosinophil and T cell responses than WT mice, correlating with accumulated chitin in the lungs. In a viral model with influenza A infection, hChia mice maintained heightened immune activation during the tissue repair phase, further demonstrating a prolonged inflammatory response. These findings suggest that impaired chitinase activity amplifies airway inflammation, possibly increasing susceptibility to asthma and other allergic conditions. This model underscores the critical role of chitin clearance in maintaining immune balance and highlights AMCase as a potential therapeutic target. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)