Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia

Mitchell H. Grayson, Dorothy Cheung, Michelle M. Rohlfing, Robert Kitchens, Daniel E. Spiegel, Jennifer Tucker, John T. Battaile, Yael Alevy, Le Yan, Eugene Agapov, Edy Y. Kim, Michael J. Holtzman

Research output: Contribution to journalArticle

153 Scopus citations

Abstract

Respiratory viral infections are associated with an increased risk of asthma, but how acute Th1 antiviral immune responses lead to chronic inflammatory Th2 disease remains undefined. We define a novel pathway that links transient viral infection to chronic lung disease with dendritic cell (DC) expression of the high-affinity IgE receptor (FcεRIα). In a mouse model of virus-induced chronic lung disease, in which Sendai virus triggered a switch to persistent mucous cell metaplasia and airway hyperreactivity after clearance of replicating virus, we found that FceRIa-/- mice no longer developed mucous cell metaplasia. Viral infection induced IgE-independent, type I IFN receptor - dependent expression of FcεRIα on mouse lung DCs. Cross-linking DC FcεRIα resulted in the production of the T cell chemoattractant CCL28. FceRIa-/- mice had decreased CCL28 and recruitment of IL-13-producing CD4+ T cells to the lung after viral infection. Transfer of wild-type DCs to FceRIa -/- mice restored these events, whereas blockade of CCL28 inhibited mucous cell metaplasia. Therefore, lung DC expression of FcεRIα is part of the antiviral response that recruits CD4+ T cells and drives mucous cell metaplasia, thus linking antiviral responses to allergic/asthmatic Th2 responses. JEM

Original languageEnglish (US)
Pages (from-to)2759-2769
Number of pages11
JournalJournal of Experimental Medicine
Volume204
Issue number11
DOIs
StatePublished - Oct 29 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Grayson, M. H., Cheung, D., Rohlfing, M. M., Kitchens, R., Spiegel, D. E., Tucker, J., Battaile, J. T., Alevy, Y., Yan, L., Agapov, E., Kim, E. Y., & Holtzman, M. J. (2007). Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia. Journal of Experimental Medicine, 204(11), 2759-2769. https://doi.org/10.1084/jem.20070360