AUTHOR=Michaudel Chloé , Bataille Florent , Maillet Isabelle , Fauconnier Louis , Colas Cyril , Sokol Harry , Straube Marjolène , Couturier-Maillard Aurélie , Dumoutier Laure , van Snick Jacques , Quesniaux Valérie F. , Togbe Dieudonnée , Ryffel Bernhard 

TITLE=Ozone-Induced Aryl Hydrocarbon Receptor Activation Controls Lung Inflammation via Interleukin-22 Modulation

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00144

DOI=10.3389/fimmu.2020.00144

ISSN=1664-3224

ABSTRACT=<p>Airborne ozone exposure causes severe lung injury and inflammation. The aryl hydrocarbon Receptor (AhR) (<xref ref-type="bibr" rid="B1">1</xref>), activated in pollutant-induced inflammation, is critical for cytokine production, especially IL-22 and IL-17A. The role of AhR in ozone-induced lung inflammation is unknown. We report here that chronic ozone exposure activates AhR with increased tryptophan and lipoxin A4 production in mice. AhR<sup>−/−</sup> mice show increased lung inflammation, airway hyperresponsiveness, and tissue remodeling with an increased recruitment of IL-17A and IL-22-expressing cells in comparison to control mice. IL-17A- and IL-22-neutralizing antibodies attenuate lung inflammation in AhR<sup>−/−</sup> and control mice. Enhanced lung inflammation and recruitment of ILC3, ILC2, and T cells were observed after T cell-specific AhR depletion using the AhR<sup>CD4cre</sup>-deficient mice. Together, the data demonstrate that ozone exposure activates AhR, which controls lung inflammation, airway hyperresponsiveness, and tissue remodeling via the reduction of IL-22 expression.</p>