IL-17a Induces Age-Related Olfactory Dysfunction by Impairing Regeneration and Promoting Respiratory Metaplasia in Mice

This study investigates the role of interleukin-17a (IL-17a) in age-related olfactory dysfunction using mouse models. It reveals that inflamm-aging, characterized by increased IL-17a expression, impairs olfactory function by disrupting olfactory epithelium (OE) regeneration and promoting respiratory metaplasia. The study demonstrates that inhibiting IL-17a with Y-320 or a neutralizing antibody enhances sensory neuronal regeneration and reverses age-related changes in the OE. Co-culturing OE organoids with Th17 cells impairs neuronal generation, but this effect is alleviated by IL-17a neutralization. Additionally, IL-17a knockout in T cells supports OE regeneration by enhancing the recruitment and differentiation of basal cells. These findings suggest IL-17a as a potential therapeutic target for age-related olfactory deficits.