Differential Regulation of the Asthmatic Phenotype by the Aryl Hydrocarbon Receptor

Hussein Traboulsi; Angela Rico de Souza; Benoit Allard; Zahraa Haidar; Mark Sorin; Vanessa Moarbes; Elizabeth D Fixman; James G Martin; David H Eidelman; Carolyn J Baglole

doi:10.3389/fphys.2021.720196

Differential Regulation of the Asthmatic Phenotype by the Aryl Hydrocarbon Receptor

Front Physiol. 2021 Oct 21:12:720196. doi: 10.3389/fphys.2021.720196. eCollection 2021.

Authors

Hussein Traboulsi^{1

2

3}, Angela Rico de Souza^{1

2}, Benoit Allard¹, Zahraa Haidar^{1

2

3}, Mark Sorin^{1

2

3}, Vanessa Moarbes^{1

2

3}, Elizabeth D Fixman^{1

2

3}, James G Martin^{1

2

3}, David H Eidelman^{1

2

3}, Carolyn J Baglole^{1

2

3

4

5}

Affiliations

¹ Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
² Translational Research in Respiratory Diseases Program at the Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
³ Department of Medicine, McGill University, Montreal, QC, Canada.
⁴ Department of Pathology, McGill University, Montreal, QC, Canada.
⁵ Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates the metabolism of xenobiotics. There is growing evidence that the AhR is implicated in physiological processes such proliferation, differentiation, and immune responses. Recently, a role of the AhR in regulating allergic asthma has been suggested, but whether the AhR also regulates other type of asthma, particularly occupational/irritant-induced asthma, remains unknown. Using AhR-deficient (Ahr^-/- ) mice, we compared the function of the AhR in the response to ovalbumin (OVA; allergic asthma) vs. chlorine (Cl₂; irritant-induced asthma) exposure. Lung inflammation and airway hyperresponsiveness were assessed 24h after exposure to Cl₂ or OVA challenge in Ahr^-/- and heterozygous (Ahr^+/- ) mice. After OVA challenge, absence of AhR was associated with significantly enhanced eosinophilia and lymphocyte influx into the airways of Ahr^-/- mice. There were also increased levels of interleukin-4 (IL-4) and IL-5 in the airways. However, OVA-induced airway hyperresponsiveness was not affected. In the irritant-induced asthma model caused by exposure to Cl₂, the AhR did not regulate the inflammatory response. However, absence of AhR reduced Cl₂-induced airway hyperresponsiveness. Collectively, these results support a differential role for the AhR in regulating asthma outcomes in response to diverse etiological agents.

Keywords: allergic asthma; aryl hydrocarbon receptor; chlorine; inflammation; lungs; neutrophils; occupational asthma.