Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17

J Exp Med. 2008 Feb 18;205(2):385-93. doi: 10.1084/jem.20071507. Epub 2008 Feb 4.

Abstract

Exposure to ozone, which is a major component of air pollution, induces a form of asthma that occurs in the absence of adaptive immunity. Although ozone-induced asthma is characterized by airway neutrophilia, and not eosinophilia, it is nevertheless associated with airway hyperreactivity (AHR), which is a cardinal feature of asthma. Because AHR induced by allergens requires the presence of natural killer T (NKT) cells, we asked whether ozone-induced AHR had similar requirements. We found that repeated exposure of wild-type (WT) mice to ozone induced severe AHR associated with an increase in airway NKT cells, neutrophils, and macrophages. Surprisingly, NKT cell-deficient (CD1d(-/-) and Jalpha18(-/-)) mice failed to develop ozone-induced AHR. Further, treatment of WT mice with an anti-CD1d mAb blocked NKT cell activation and prevented ozone-induced AHR. Moreover, ozone-induced, but not allergen-induced, AHR was associated with NKT cells producing interleukin (IL)-17, and failed to occur in IL-17(-/-) mice nor in WT mice treated with anti-IL-17 mAb. Thus, ozone exposure induces AHR that requires the presence of NKT cells and IL-17 production. Because NKT cells are required for the development of two very disparate forms of AHR (ozone- and allergen-induced), our results strongly suggest that NKT cells mediate a unifying pathogenic mechanism for several distinct forms of asthma, and represent a unique target for effective asthma therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants / toxicity*
  • Animals
  • Bronchial Hyperreactivity / chemically induced
  • Bronchial Hyperreactivity / immunology*
  • Bronchoalveolar Lavage Fluid / cytology
  • Disease Models, Animal
  • Interleukin-13 / deficiency
  • Interleukin-13 / genetics
  • Interleukin-13 / immunology
  • Interleukin-17 / deficiency
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukin-4 / deficiency
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Killer Cells, Natural / immunology*
  • Leukocyte Count
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / administration & dosage
  • Ozone / toxicity*
  • T-Lymphocytes / immunology*

Substances

  • Air Pollutants
  • Interleukin-13
  • Interleukin-17
  • Interleukin-4
  • Ozone
  • Ovalbumin