IFNβ inhibits the development of allergen tolerance and is conducive to the development of asthma on subsequent allergen exposure

Vanessa S. Fear, Wee Peng Poh, Shelley Gorman, Jason C. Waithman, Mark W. Fear

Research output: Contribution to journalArticle

Abstract

Asthma is a chronic disease affecting up to 10% of the Australian population for which medical treatment is solely aimed at relief of symptoms rather than prevention of disease. Evidence from animal and human studies demonstrates a strong link between viral respiratory infections, atopy and the development of asthma. Type I IFNs include IFNα and IFNβ, with subtype expression tailored toward the specific viral infection. We hypothesized that exposure to type I IFNs and allergen may interfere with the healthy response to innocuous airway antigen exposure. In this study, we use an ovalbumin (OVA)-induced BALB/c model of experimental allergic airways disease, where pre-exposure of the airways to OVA is protective against allergen sensitization, leading to allergen tolerance. We investigated airways pre-exposure with OVA and type I IFNs on development of allergic airways disease. We demonstrate restoration of allergic airways disease on pre-exposure with allergen and IFNβ, and not IFNα. Dysfunction in tolerance led to changes in dendritic cell antigen capture/traffic, T-cell and B-cell responses. Furthermore, exposure to IFNβ with ongoing allergen exposure led to the development of hallmark asthma features, including OVA-specific IgE and airways eosinophilia. Data indicate a role for IFNβ in linking viral infection and allergy.

Original languageEnglish
Pages (from-to)841-851
JournalImmunology and Cell Biology
Volume96
Issue number8
Early online date17 Apr 2018
DOIs
Publication statusPublished - Sep 2018

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Allergens
Ovalbumin
Asthma
Virus Diseases
Antigens
Eosinophilia
Respiratory Tract Infections
Dendritic Cells
Immunoglobulin E
Hypersensitivity
B-Lymphocytes
Chronic Disease
Theoretical Models
T-Lymphocytes
Population

Cite this

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title = "IFNβ inhibits the development of allergen tolerance and is conducive to the development of asthma on subsequent allergen exposure",
abstract = "Asthma is a chronic disease affecting up to 10{\%} of the Australian population for which medical treatment is solely aimed at relief of symptoms rather than prevention of disease. Evidence from animal and human studies demonstrates a strong link between viral respiratory infections, atopy and the development of asthma. Type I IFNs include IFNα and IFNβ, with subtype expression tailored toward the specific viral infection. We hypothesized that exposure to type I IFNs and allergen may interfere with the healthy response to innocuous airway antigen exposure. In this study, we use an ovalbumin (OVA)-induced BALB/c model of experimental allergic airways disease, where pre-exposure of the airways to OVA is protective against allergen sensitization, leading to allergen tolerance. We investigated airways pre-exposure with OVA and type I IFNs on development of allergic airways disease. We demonstrate restoration of allergic airways disease on pre-exposure with allergen and IFNβ, and not IFNα. Dysfunction in tolerance led to changes in dendritic cell antigen capture/traffic, T-cell and B-cell responses. Furthermore, exposure to IFNβ with ongoing allergen exposure led to the development of hallmark asthma features, including OVA-specific IgE and airways eosinophilia. Data indicate a role for IFNβ in linking viral infection and allergy.",
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