Interferon at the crossroads of allergy and viral infections

Sarah R. Gonzales-van Horn, J. David Farrar

Research output: Contribution to journalReview articlepeer-review

24 Scopus citations

Abstract

IFN-α/β was first described as a potent inhibitor of viral replication, but it is now appreciated that IFN signaling plays a pleiotropic role in regulating peripheral T cell functions. Recently, IFN-α/β was shown to block human Th2 development by suppressing the transcription factor GATA3. This effect is consistent with the role for IFN-α/β in suppressing allergic inflammatory processes by blocking granulocyte activation and IL-4-mediated B cell isotype switching to IgE. With the consideration of recent studies demonstrating a defect in IFN-α/β secretion in DCs and epithelial cells from individuals with severe atopic diseases, there is an apparent reciprocal negative regulatory loop in atopic individuals, whereby the lack of IFN-α/β secretion by innate cells contributes to the development of allergic Th2 cells. Is it possible to overcome these events by treating with IFN-α/β or by inducing its secretion in vivo? In support of this approach, case studies have documented the therapeutic potential of IFN-α/β in treating steroid-resistant allergic asthma and other atopic diseases. Additionally, individuals with asthma who are infected with HCV and respond to IFN therapy showed a reduction in symptoms and severity of asthma attacks. These findings support a model, whereby allergic and antiviral responses are able to cross-regulate each other, as IgER cross-linking of pDCs prevents IFN-α/β production in response to viral infection. The clinical importance of upper-respiratory viruses in the context of allergic asthma supports the need to understand how these pathways intersect and to identify potential therapeutic targets.

Original languageEnglish (US)
Pages (from-to)185-194
Number of pages10
JournalJournal of Leukocyte Biology
Volume98
Issue number2
DOIs
StatePublished - Aug 1 2015

Keywords

  • Atopic asthma
  • Atopic disease
  • IgE-mediated regulation
  • Th2 cell regulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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