Pharmacological AhR Activation Attenuates Airway Hyperresponsiveness and Remodeling in a Mixed Allergen Asthma Model.

Pharmacological activation of AhR with a high-affinity agonist, TCDD , significantly improved lung function, attenuated airway narrowing in precision-cut lung slices, and reduced markers of airway remodeling. Bulk lung transcriptomic profiling revealed robust activation of inflammatory and immune-associated gene programs in MA-exposed mice, characterized by enrichment of chemokine, cytokine, neutrophil recruitment, and tissue remodeling pathways.

In contrast, AhR activation in MA-exposed mice suppressed these inflammatory networks, reduced expression of key upstream and downstream mediators, and normalized multiple disease-relevant pathways. TCDD treatment alone induced classical AhR target genes without broadly activating inflammatory programs. Collectively, these findings demonstrate that AhR activation suppresses inflammatory gene networks, limits airway remodeling, and improves airway mechanics in MA-induced asthma.