Pharmacological AhR activation attenuates airway hyperresponsiveness and remodeling in a mixed allergen asthma model
Abstract
Airway hyperresponsiveness and remodeling are major features of asthma. We investigated whether pharmacological activation of the aryl hydrocarbon receptor (AhR) modifies these responses in a mixed allergen (MA) mouse model of asthma. MA exposure increased airway resistance, contractility, inflammation, and remodeling, with elevated AhR expression in whole lung and airway smooth muscle but limited canonical AhR target gene activation. Treatment with the high-affinity AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) improved lung mechanics, reduced inflammatory cell and cytokine accumulation, attenuated airway remodeling, and decreased airway narrowing in precision-cut lung slices. Bulk lung RNA sequencing further showed suppression of inflammatory, neutrophil-associated, and remodeling pathways following TCDD treatment, together with induction of canonical AhR target genes. Collectively, these findings demonstrate that AhR activation suppresses inflammatory gene networks, limits airway remodeling, and improves airway mechanics in experimental asthma, supporting the therapeutic potential of targeting AhR signaling to mitigate airway dysfunction and structural remodeling.
Related
- Longitudinal Left Atrial Remodeling With Pharmacological Rhythm Versus Rate Control in Paroxysmal and Persistent Atrial Fibrillation
- Group IVA Cytosolic Phospholipase A2 (cPLA2α): Pharmacological Inhibition Attenuates Kidney Inflammation and Fibrosis
- Pharmacological Antagonism of HTR2B Reduces ERK and STAT3 Activation and Prevents Renal Fibrosis During the Development of Adenine-Induced CKD in Rats
- Intratracheal Administration of Benzbromarone Attenuates Pulmonary Vascular Remodeling and Improves Survival in Rats with Monocrotaline-Induced Pulmonary Hypertension
- AICAR attenuates senescence-associated phenotypic remodeling of liver sinusoidal endothelial cells via the AMPK–SIRT1/p53 axis in CCl₄-induced liver fibrosis
BibTeX
@article{reza2026pharmacological,
title = {{Pharmacological AhR activation attenuates airway hyperresponsiveness and remodeling in a mixed allergen asthma model}},
author = {Mohammad Irshad Reza and Premanand Balraj and Ashish Kumar and Kathryn M. Heyob and Joshua Walum and Rodney D. Britt and Venkatachalem Sathish},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117842},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03223-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pharmacological AhR activation attenuates airway hyperresponsiveness and remodeling in a mixed allergen asthma model
AU - Mohammad Irshad Reza
AU - Premanand Balraj
AU - Ashish Kumar
AU - Kathryn M. Heyob
AU - Joshua Walum
AU - Rodney D. Britt
AU - Venkatachalem Sathish
PY - 2026
DA - 2026/10/16
JO - iScience
DO - 10.1016/j.isci.2026.117842
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03223-2
AB - Airway hyperresponsiveness and remodeling are major features of asthma. We investigated whether pharmacological activation of the aryl hydrocarbon receptor (AhR) modifies these responses in a mixed allergen (MA) mouse model of asthma. MA exposure increased airway resistance, contractility, inflammation, and remodeling, with elevated AhR expression in whole lung and airway smooth muscle but limited canonical AhR target gene activation. Treatment with the high-affinity AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) improved lung mechanics, reduced inflammatory cell and cytokine accumulation, attenuated airway remodeling, and decreased airway narrowing in precision-cut lung slices. Bulk lung RNA sequencing further showed suppression of inflammatory, neutrophil-associated, and remodeling pathways following TCDD treatment, together with induction of canonical AhR target genes. Collectively, these findings demonstrate that AhR activation suppresses inflammatory gene networks, limits airway remodeling, and improves airway mechanics in experimental asthma, supporting the therapeutic potential of targeting AhR signaling to mitigate airway dysfunction and structural remodeling.
SN - 2589-0042
ER -