ozone exposure, air pollution, asthma, airway neutrophilia, killer T cells, IL-17
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 Jα18-/-) 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.
Original Publication Citation
Pichavant, M., S. Goya, E. H. Meyer, R. A. Johnston, H. Y. Kim, P. Matangkasombut, M. Zhu, Y. Iwakura, P. B. Savage, R. H. Dekruyff, S. A. Shore, and D. T. Umetsu (28, February). Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer t cells and il-17. J. Exp. Med. 25 (2), 385-393.
BYU ScholarsArchive Citation
Savage, Paul B.; Pichavant, Muriel; Goya, Sho; Meyer, Everett H.; Johnston, Richard A.; Kim, Hye Y.; Matangkasombut, Ponpan; Zhu, Ming; Iwakura, Yoichiro; DeKruyff, Rosemarie H.; Shore, Stephanie A.; and Umetsu, Dale T., "Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17" (2008). All Faculty Publications. 204.
The Rockefeller University Press
Physical and Mathematical Sciences
Chemistry and Biochemistry
© 2008 Pichavant et al.
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