title: Interferon at the crossroads of allergy and viral infections.
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.
authors.affiliation: Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Gonzales-van Horn
authors.affiliation: Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA david.farrar@utsouthwestern.edu.
authors.forename: J David
authors.initials: JD
authors.lastname: Farrar
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D050990:GATA3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000235:genetics; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D014777:Virus Diseases / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C508598:IL4 protein, human; D016898:Interferon-alpha; D015847:Interleukin-4; D007073:Immunoglobulin E; D016899:Interferon-beta
keywords: IgE-mediated regulation; Th2 cell regulation; atopic asthma; atopic disease