Interferon at the crossroads of allergy and viral infections
Open Access
- 29 May 2015
- journal article
- review article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 98 (2), 185-194
- https://doi.org/10.1189/jlb.3ru0315-099r
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.Keywords
Funding Information
- Crystal Charity Ball
- J.D.F.
- National Institutes of Health (AIF31094800)
- S.R.G.-v.H. (AIT32005284)
- J.D.F. (AIR0156222)
This publication has 101 references indexed in Scilit:
- IL-25 drives remodelling in allergic airways disease induced by house dust miteThorax, 2012
- Rhinoviruses, allergic inflammation, and asthmaImmunological Reviews, 2011
- Regulation of effector and memory T-cell functions by type I interferonImmunology, 2011
- The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammationNature Immunology, 2010
- Rhinovirus-induced modulation of gene expression in bronchial epithelial cells from subjects with asthmaMucosal Immunology, 2009
- In vitro susceptibility to rhinovirus infection is greater for bronchial than for nasal airway epithelial cells in human subjectsJournal of Allergy and Clinical Immunology, 2009
- Unique and overlapping gene expression patterns driven by IL-4 and IL-13 in the mouse lungJournal of Allergy and Clinical Immunology, 2009
- Interferon-inducible antiviral effectorsNature Reviews Immunology, 2008
- The Presence of Rhinovirus in Lower Airways of Patients with Bronchial AsthmaAmerican Journal of Respiratory and Critical Care Medicine, 2008
- Insights into the Interaction between Influenza Virus and PneumococcusClinical Microbiology Reviews, 2006