Kynurenic acid attenuates experimental allergic rhinitis: Evidence for AhR-associated regulation of mucosal immune homeostasis
- 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran
- 2Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran
Abstract
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.
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BibTeX
@article{gheymoumi2026kynurenic,
title = {{Kynurenic acid attenuates experimental allergic rhinitis: Evidence for AhR-associated regulation of mucosal immune homeostasis}},
author = {Naim Gheymoumi and Sevda Shayesteh and Fatemeh Sharifi and Marziyeh Amiri-Andebili and Hediyeh Gheymoumi},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0359624},
url = {https://doi.org/10.1371/journal.pone.0359624},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Kynurenic acid attenuates experimental allergic rhinitis: Evidence for AhR-associated regulation of mucosal immune homeostasis
AU - Naim Gheymoumi
AU - Sevda Shayesteh
AU - Fatemeh Sharifi
AU - Marziyeh Amiri-Andebili
AU - Hediyeh Gheymoumi
PY - 2026
DA - 2026/10/01
JO - PLOS One
DO - 10.1371/journal.pone.0359624
UR - https://doi.org/10.1371/journal.pone.0359624
AB - 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.
SN - 1932-6203
ER -