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 AhR^CD4cre-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.

空气中的臭氧暴露会导致严重的肺损伤和炎症。芳烃受体 (AhR) ( 1 ）在污染物引起的炎症中被激活，对于细胞因子的产生至关重要，尤其是 IL-22 和 IL-17A。 AhR 在臭氧引起的肺部炎症中的作用尚不清楚。我们在这里报告，长期暴露于臭氧会激活 AhR，增加小鼠色氨酸和脂氧素 A4 的产生。与对照小鼠相比，AhR ^-/−小鼠表现出肺部炎症增加、气道高反应性和组织重塑，并且表达 IL-17A 和 IL-22 的细胞募集增加。 IL-17A 和 IL-22 中和抗体可减轻 AhR ^−/−和对照小鼠的肺部炎症。使用 AhR ^CD4cre缺陷型小鼠去除 T 细胞特异性 AhR 后，观察到肺部炎症增强以及 ILC3、ILC2 和 T 细胞的募集。总之，数据表明，臭氧暴露会激活 AhR，后者通过减少 IL-22 表达来控制肺部炎症、气道高反应性和组织重塑。