Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma

Douglas A. Kuperman, Xiaozhu Huang, Laura L. Koth, Grace H. Chang, Gregory M. Dolganov, Zhou Zhu, Jack A. Elias, Dean Sheppard, David J. Erle

Research output: Contribution to journalArticle

Abstract

Asthma is an increasingly common disease that remains poorly understood and difficult to manage. This disease is characterized by airway hyperreactivity (AHR, defined by exaggerated airflow obstruction in response to bronchoconstrictors), mucus overproduction and chronic eosinophilic inflammation1. AHR and mucus overproduction are consistently linked to asthma symptoms and morbidity2, 3. Asthma is mediated by Th2 lymphocytes4-7, which produce a limited repertoire of cytokines, including interleukin-4 (IL-4), IL-5, IL-9 and IL-13. Although each of these cytokines has been implicated in asthma4, 5, 7-11, IL-13 is now thought to be especially critical. In animal models of allergic asthma, blockade of IL-13 markedly inhibits allergen-induced AHR, mucus production and eosinophilia10, 11. Furthermore, IL-13 delivery to the airway causes all of these effects10, 11. IL-13 is thus both necessary and sufficient for experimental models of asthma. However, the IL-13-responsive cells causing these effects have not been identified. Here we show that mice lacking signal transducer and activator of transcription 6 (STAT6) were protected from all pulmonary effects of IL-13. Reconstitution of STAT6 only in epithelial cells was sufficient for IL-13-induced AHR and mucus production in the absence of inflammation, fibrosis or other lung pathology. These results demonstrate the importance of direct effects of IL-13 on epithelial cells in causing two central features of asthma.

Original languageEnglish (US)
Pages (from-to)885-889
Number of pages5
JournalNature medicine
Volume8
Issue number8
DOIs
StatePublished - Aug 2002

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kuperman, D. A., Huang, X., Koth, L. L., Chang, G. H., Dolganov, G. M., Zhu, Z., Elias, J. A., Sheppard, D., & Erle, D. J. (2002). Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. Nature medicine, 8(8), 885-889. https://doi.org/10.1038/nm734