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BACKGROUND: Ozone increases IL-33 in the lungs, and obesity augments the pulmonary effects of acute ozone exposure.

OBJECTIVES: We assessed the role of IL-33 in the augmented effects of ozone observed in obese mice.

METHODS: Lean wildtype and obese db/db mice were pretreated with antibodies blocking the IL-33 receptor, ST2, and then exposed to ozone (2 ppm for 3 hr). Airway responsiveness was assessed, bronchoalveolar lavage (BAL) was performed, and lung cells harvested for flow cytometry 24 hr later. Effects of ozone were also assessed in obese and lean mice deficient in.gamma delta T cells and their wildtype controls.

RESULTS AND DISCUSSION: Ozone caused greater increases in BAL IL-33, neutrophils, and airway responsiveness in obese than lean mice. Anti-ST2 reduced ozone-induced airway hyperresponsiveness and inflammation in obese mice but had no effect in lean mice. Obesity also augmented ozone-induced increases in BAL CXCL1 and IL-6, and in BAL type 2 cytokines, whereas anti-ST2 treatment reduced these cytokines. In obese mice, ozone increased lung IL-13(+) innate lymphoid cells type 2 (ILC2) and IL-13(+).gamma delta T cells. Ozone increased ST2(+) gamma delta T cells, indicating that these cells can be targets of IL-33, and.gamma delta T cell deficiency reduced obesity-related increases in the response to ozone, including increases in type 2 cytokines.

CONCLUSIONS: Our data indicate that IL-33 contributes to augmented responses to ozone in obese mice. Obesity and ozone also interacted to promote type 2 cytokine production in.gamma delta T cells and ILC2 in the lungs, which may contribute to the observed effects of IL-33.