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Environ Health Perspect. 2017 Feb;125(2):246-253. doi: 10.1289/EHP272. Epub 2016 Jul 29.

IL-33 Drives Augmented Responses to Ozone in Obese Mice.

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Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.



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


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


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 γδ T cells and their wildtype controls.


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+ γδ T cells. Ozone increased ST2+ γδ T cells, indicating that these cells can be targets of IL-33, and γδ T cell deficiency reduced obesity-related increases in the response to ozone, including increases in type 2 cytokines.


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 γδ T cells and ILC2 in the lungs, which may contribute to the observed effects of IL-33. Citation: Mathews JA, Krishnamoorthy N, Kasahara DI, Cho Y, Wurmbrand AP, Ribeiro L, Smith D, Umetsu D, Levy BD, Shore SA. 2017. IL-33 drives augmented responses to ozone in obese mice. Environ Health Perspect 125:246-253;

[Indexed for MEDLINE]
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Conflict of interest statement

J.A.M. is currently an employee of Genentech, South San Francisco, California (post completion of research), D.S. is a former employee of Amgen, Seattle, Washington (developer of the anti-ST2 antibody for both preclinical and clinical development), and D.U. is an employee of Genentech (current owner and developer of the clinical anti-ST2 antibody. The anti-ST2 antibody is being developed for use in asthma patients). The authors declare they have no actual or potential financial interests.

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