IL-17a induces age-related olfactory dysfunction by impairing regeneration and promoting respiratory metaplasia in mice.

Summary

Using aged mice, organoids, and genetic models, the authors show that IL-17a drives inflamm-aging in the olfactory epithelium, impairing neuronal regeneration and inducing respiratory metaplasia. Pharmacologic and genetic IL-17a blockade restores regeneration and olfactory epithelial composition, nominating IL-17a as a therapeutic target for presbyosmia.

Key Findings

• Aged olfactory epithelium exhibits increased IL-17a, immune cell recruitment, and HBC–T cell crosstalk, impairing olfactory function.
• IL-17a inhibitor Y-320 or neutralizing antibody promoted sensory neuronal regeneration and reversed age-related respiratory metaplasia in the OE.
• Th17 co-culture reduced neuronal generation and increased respiratory cell transformation; anti-IL-17a rescued these effects, and T cell–specific IL-17a knockout enhanced HBC recruitment and differentiation into GBC.

Clinical Implications

IL-17a antagonism (potentially via topical intranasal approaches) could be explored to treat presbyosmia, though careful safety evaluation is needed given systemic immune roles.

Limitations

• Preclinical mouse study; human translatability and long-term safety of IL-17a inhibition remain unproven.
• Molecular pathways downstream of IL-17a that govern HBC–GBC transitions are not fully delineated.

Future Directions

Test topical IL-17a blockade in translational models and early-phase human studies; map downstream pathways controlling basal cell fate to refine targeted interventions.