| First Author | Nguyen TH | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 1 | Pages | 237-247 |
| PubMed ID | 29167232 | Mgi Jnum | J:253426 |
| Mgi Id | MGI:6108035 | Doi | 10.4049/jimmunol.1601950 |
| Citation | Nguyen TH, et al. (2018) Identification of IFN-gamma and IL-27 as Critical Regulators of Respiratory Syncytial Virus-Induced Exacerbation of Allergic Airways Disease in a Mouse Model. J Immunol 200(1):237-247 |
| abstractText | 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-gamma and IL-27 in the regulation of RSV-induced exacerbation of allergic airways disease. Production of IFN-gamma and IL-27 was steroid-resistant, and neutralization of IFN-gamma or IL-27 significantly suppressed RSV-induced steroid-resistant airway hyperresponsiveness and airway inflammation. We have previously implicated activation of pulmonary macrophage by TNF-alpha and/or MCP-1 in the mechanisms of RSV-induced exacerbation. Stimulation of pulmonary macrophages with TNF-alpha and/or MCP-1 induced expression of both IFN-gamma and IL-27. Our findings highlight critical roles for IFN-gamma and IL-27, downstream of TNF-alpha 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. |
