- Title
- Identification of IFN-γ and IL-27 as critical regulators of respiratory syncytial virus-induced exacerbation of allergic airways disease in a mouse model
- Creator
- Nguyen, Thi Hiep; Maltby, Steven; Tay, Hock L.; Eyers, Fiona; Foster, Paul S.; Yang, Ming
- Relation
- Journal of Immunology Vol. 200, Issue 1, p. 237-247
- Publisher Link
- http://dx.doi.org/10.4049/jimmunol.1601950
- Publisher
- American Association of Immunologists
- Resource Type
- journal article
- Date
- 2018
- Description
- Respiratory syncytial virus (RSV) infection induces asthma exacerbations, which leads to worsening of clinical symptoms and may result in a sustained decline in lung function. Exacerbations are the main cause of morbidity and mortality associated with asthma, and significantly contribute to asthma-associated healthcare costs. Although glucocorticoids are used to manage exacerbations, some patients respond to them poorly. The underlying mechanisms associated with steroid-resistant exacerbations remain largely unknown. We have previously established a mouse model of RSV-induced exacerbation of allergic airways disease, which mimics hallmark clinical features of asthma. In this study, we have identified key roles for macrophage IFN-γ and IL-27 in the regulation of RSV-induced exacerbation of allergic airways disease. Production of IFN-γ and IL-27 was steroid-resistant, and neutralization of IFN-γ or IL-27 significantly suppressed RSV-induced steroid-resistant airway hyperresponsiveness and airway inflammation. We have previously implicated activation of pulmonary macrophage by TNF-a and/or MCP-1 in the mechanisms of RSV-induced exacerbation. Stimulation of pulmonary macrophages with TNF-a and/or MCP-1 induced expression of both IFN-γ and IL-27. Our findings highlight critical roles for IFN-γ and IL-27, downstream of TNF-a and MCP-1, in the mechanism of RSV-induced exacerbation. Thus, targeting the pathways that these factors activate may be a potential therapeutic approach for virus-induced asthma exacerbations.
- Subject
- respiratory syncytial virus; asthma; lung function; IFN-γ; IL-27
- Identifier
- http://hdl.handle.net/1959.13/1390567
- Identifier
- uon:33087
- Identifier
- ISSN:0022-1767
- Language
- eng
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