title: IL-33 Drives Augmented Responses to Ozone in Obese Mice.
abstract: 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; http://dx.doi.org/10.1289/EHP272.
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Mathews
authors.forename: Nandini
authors.initials: N
authors.lastname: Krishnamoorthy
authors.forename: David Itiro
authors.initials: DI
authors.lastname: Kasahara
authors.forename: Youngji
authors.initials: Y
authors.lastname: Cho
authors.forename: Allison Patricia
authors.initials: AP
authors.lastname: Wurmbrand
authors.forename: Luiza
authors.initials: L
authors.lastname: Ribeiro
authors.forename: Dirk
authors.initials: D
authors.lastname: Smith
authors.forename: Dale
authors.initials: D
authors.lastname: Umetsu
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Levy
authors.forename: Stephanie Ann
authors.initials: SA
authors.lastname: Shore
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D018793:Interleukin-13 / Q000378:metabolism*; D051379:Mice; D010126:Ozone / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D000393:Air Pollutants; D018793:Interleukin-13; D010126:Ozone