Kynurenic acid attenuates experimental allergic rhinitis: Evidence for AhR-associated regulation of mucosal immune homeostasis.

BACKGROUND

Allergic rhinitis (AR) is a chronic inflammatory airway disease characterized by dysregulated type 2 immune responses and impaired mucosal immune regulation. Kynurenic acid (KYNA), an endogenous tryptophan metabolite with immunomodulatory properties, may influence inflammatory pathways, but its mechanisms in AR remain unclear. This study investigated KYNA in an ovalbumin (OVA)-induced rat model of AR and examined the role of aryl hydrocarbon receptor (AhR) signaling.

METHODS

Rats were assigned to control, AR, vehicle, KYNA, desloratadine, and KYNA + AhR antagonist (CH223191) groups. Following OVA sensitization and challenge, behavioral responses, serum inflammatory markers, nasal AhR-associated proteins, regulatory cytokines, and histopathological changes in nasal and splenic tissues were evaluated.

RESULTS

OVA induced typical allergic responses, including increased sneezing and nasal scratching, elevated serum IgE, IL-4, and IL-6, and marked inflammatory changes in nasal and splenic tissues. KYNA significantly reduced behavioral symptoms, systemic inflammatory mediators, epithelial damage, and inflammatory infiltration, with systemic effects comparable to desloratadine but greater improvement in nasal scratching and splenic histopathology. KYNA restored nasal AhR and CYP1A1 expression and increased IL-10 and TGF-β, whereas CH223191 partially attenuated these effects, indicating involvement of AhR signaling. Desloratadine showed limited effects on local regulatory cytokines. Histopathological analysis confirmed improved nasal and splenic architecture following KYNA treatment.

CONCLUSION

In conclusion, KYNA attenuates experimental AR through systemic anti-inflammatory effects and restoration of mucosal immune regulation. AhR signaling contributes to these effects, particularly in CYP1A1 and cytokine regulation, while additional mechanisms may also be involved. These findings support KYNA as a potential immunometabolic modulator in allergic airway disease.