Interferon at the crossroads of allergy and viral infections

J Leukoc Biol. 2015 Aug;98(2):185-94. doi: 10.1189/jlb.3RU0315-099R. Epub 2015 May 29.


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.

Keywords: IgE-mediated regulation; Th2 cell regulation; atopic asthma; atopic disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • B-Lymphocytes / virology
  • GATA3 Transcription Factor / antagonists & inhibitors
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / immunology
  • Gene Expression Regulation
  • Granulocytes / drug effects
  • Granulocytes / immunology
  • Granulocytes / pathology
  • Granulocytes / virology
  • Humans
  • Hypersensitivity / drug therapy
  • Hypersensitivity / immunology*
  • Hypersensitivity / pathology
  • Hypersensitivity / virology
  • Immunoglobulin Class Switching
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin E / genetics
  • Interferon-alpha / genetics
  • Interferon-alpha / immunology*
  • Interferon-alpha / therapeutic use
  • Interferon-beta / genetics
  • Interferon-beta / immunology*
  • Interferon-beta / therapeutic use
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Signal Transduction
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Th2 Cells / pathology
  • Th2 Cells / virology
  • Virus Diseases / drug therapy
  • Virus Diseases / immunology*
  • Virus Diseases / pathology
  • Virus Diseases / virology


  • GATA3 Transcription Factor
  • GATA3 protein, human
  • IL4 protein, human
  • Interferon-alpha
  • Interleukin-4
  • Immunoglobulin E
  • Interferon-beta