J Leukoc Biol 98(2): 185-194

Interferon at the crossroads of allergy and viral infections

Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA

^{Correspondence: Dept. of Immunology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9093, USA. E-mail:}ude.nretsewhtuostu@rarraf.divad

Received 2015 Mar 9; Revised 2015 May 7; Accepted 2015 May 12.

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: atopic asthma, Th2 cell regulation, IgE-mediated regulation, atopic disease

Abstract

ER, emergency room; FEV1, forced expiratory volume in 1 s; MBP, major basic protein.

Acknowledgments

Funding for this work was supported by the Crystal Charity Ball (to J.D.F.) and by the U.S. National Institutes of Health Grants AIF31094800 and AIT32005284 (to S.R.G.-v.H.) and AIR0156222 (to J.D.F.). The authors thank Didem Agac for critical review of this manuscript.

Acknowledgments

Glossary

CNS-1	conserved noncoding sequence
DC	conventional dendritic cell
GAS	γ−activated sequence
H3	histone 3
H3K27me3	histone 3 lysine 27 trimethylation
HCV	hepatitis C virus
IFN-α/β	type I IFN
IFN-γ	type II IFN
IFN-λ	type III IFN
ILC1/2	innate lymphoid type 1/2 cell
IRF	IFN regulatory factor
ISG	IFN-sensitive gene
ISRE	IFN-stimulated response element
pDC	plasmacytoid dendritic cell
SOCS1	suppressor of cytokine signaling 1
TSLP	thymic stromal lymphoprotein

Glossary

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