Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF) Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Pichavant, M. Articles by Umetsu, D. T. PubMed PubMed Citation Articles by Pichavant, M. Articles by Umetsu, D. T. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide Protein UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB OZONE Social Bookmarking                      What's this?

¹ Children's Hospital Boston, Harvard Medical School, Boston, MA 02115
² Harvard School of Public Health, Boston, MA 02115
³ Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
⁴ Brigham Young University, Provo, UT 84604
⁵ Stanford Immunology Program, Stanford University, Stanford, CA 94305

CORRESPONDENCE Dale T. Umetsu:dale.umetsu{at}childrens.harvard.edu

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 J18^–/–) 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.

Abbreviations used: -GalCer, -galactosylceramide; AHR, airway hyperreactivity; ppm, parts per million.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Akbari, O., Stock, P., Meyer, E. H., Freeman, G. J., Sharpe, A. H., Umetsu, D. T., DeKruyff, R. H. (2008). ICOS/ICOSL Interaction Is Required for CD4+ Invariant NKT Cell Function and Homeostatic Survival. J. Immunol. 180: 5448-5456 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS