Peroxisome Proliferator‐Activated Receptor–γ Agonist Induces Regulatory T Cells in a Murine Model of Allergic Rhinitis

Objective To evaluate the effects of peroxisome proliferator‐activated receptor (PPAR)–γ agonist on the induction of regulatory T cells (Tregs) in a murine model of allergic rhinitis. Study Design Randomized controlled trial. Setting Animal study. Subjects and Methods BALB/c mice that received ovalbumin sensitization and challenge served as the ovalbumin group (n = 6). Two separate groups of 6 mice received intragastric administration with PPAR‐γ agonist pioglitazone (30 mg/kg/d) or pioglitazone plus PPAR‐γ antagonist GW9662 (0.5 mg/d) before each ovalbumin challenge. The control group (n = 6) was treated with drug vehicle alone. Various allergic responses were assessed. Real‐time polymerase chain reaction was performed to investigate the mRNA expression of forkhead box P3 (Foxp3), T‐bet, and GATA‐3. Flow cytometry was used to determine the percentage of Tregs. Results Mice developed typical pathophysiological allergic rhinitis features after the ovalbumin challenge. The frequencies of sneezing and scratching were significantly decreased by pioglitazone treatment ( P <. 0001). Eosinophils infiltration and the levels of interleukin‐5 and interferon‐γ in nasal cavity lavage fluid and sera immunoglobulin E were also markedly decreased by pioglitazone ( P <. 001). The expression of Foxp3 mRNA and the population of Tregs were significantly increased by pioglitazone ( P <. 05). Cotreatment with GW9662 reversed the anti‐inflammatory effects of pioglitazone. The effects of PPAR‐γ agonist on Foxp3 mRNA expression and Tregs induction were abrogated by administration of GW9662. Conclusion PPAR‐γ agonist attenuates upper airway allergic inflammation in a PPAR‐γ‐dependent fashion, and the beneficial effects of pioglitazone in airway allergic inflammation may be mediated by induction of Tregs.