Interferon at the crossroads of allergy and viral infections.

ABSTRACT: IFN-?/? 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-?/? was shown to block human Th2 development by suppressing the transcription factor GATA3. This effect is consistent with the role for IFN-?/? 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-?/? 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-?/? secretion by innate cells contributes to the development of allergic Th2 cells. Is it possible to overcome these events by treating with IFN-?/? or by inducing its secretion in vivo? In support of this approach, case studies have documented the therapeutic potential of IFN-?/? 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-?/? 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.

SUBMITTER: Gonzales-van Horn SR 

PROVIDER: S-EPMC4501675 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature