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

Airborne ozone exposure causes severe lung injury and inflammation. Aryl hydrocarbon Receptor (Lee et al.), 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-/- mice show increased lung inflammation, airways hyperresponsiveness and tissue remodelling 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-/- and control mice. Enhanced lung inflammation and recruitment of ILC3, ILC2 and T cells were observed after T cell-specific AhR depletion using the AhRCD4cre deficient mice. Altogether, the data demonstrate that ozone activates AhR, which control lung inflammation, airway hyperresponsiveness and tissue remodelling via the reduction of IL-22 expression.