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

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.

• Authors: Muriel Pichavant, Sho Goya, Everett H Meyer, Richard A Johnston, Hye Y Kim, Ponpan Matangkasombut, Ming Zhu, Yoichiro Iwakura, Paul B Savage, Rosemarie H DeKruyff, Stephanie A Shore, Dale T Umetsu
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 205 Issue 2 Pg. 385-93 (Feb 18 2008) ISSN: 1540-9538 [Electronic] United States
• PMID: 18250191 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Air Pollutants (toxicity)
• Animals
• Bronchial Hyperreactivity (chemically induced, immunology)
• Bronchoalveolar Lavage Fluid (cytology)
• Disease Models, Animal
• Interleukin-13 (deficiency, genetics, immunology)
• Interleukin-17 (deficiency, genetics, immunology)
• Interleukin-4 (deficiency, genetics, 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)