Ozone-Induced Aryl Hydrocarbon Receptor Activation Controls Lung Inflammation via Interleukin-22 Modulation.
Airborne ozone exposure causes severe lung injury and inflammation. The aryl hydrocarbon Receptor (AhR) (1), 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, 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-/- 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. 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.
['Michaudel|Chloé|C|', 'Bataille|Florent|F|', 'Maillet|Isabelle|I|', 'Fauconnier|Louis|L|', 'Colas|Cyril|C|', 'Sokol|Harry|H|', 'Straube|Marjolène|M|', 'Couturier-Maillard|Aurélie|A|', 'Dumoutier|Laure|L|', 'van Snick|Jacques|J|', 'Quesniaux|Valérie F|VF|', 'Togbe|Dieudonnée|D|', 'Ryffel|Bernhard|B|']
D000818:Animals D057134:Antibodies, Neutralizing D051792:Basic Helix-Loop-Helix Transcription Factors D015496:CD4-Positive T-Lymphocytes D020381:Interleukin-17 D007378:Interleukins D044045:Lipoxins D055370:Lung Injury D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D010126:Ozone D011014:Pneumonia D018336:Receptors, Aryl Hydrocarbon D053722:Receptors, Interleukin-17 D012130:Respiratory Hypersensitivity D014364:Tryptophan
inflammation ozone AhR IL-22 ILC3 T cells IL-17