Abstract
BackgroundThe interleukin 17 receptor E (IL-17RE) is specific for the epithelial cytokine interleukin-17C (IL-17C). Asthma exacerbations are frequently caused by viral infections. Polyinosinic:polycytidylic acid (pIC) mimics viral infections through binding to pattern recognition receptors (e.g. TLR-3). We and others have shown that pIC induces the expression of IL-17C in airway epithelial cells. Using different mouse models, we aimed to investigate the function of IL-17RE in the development of experimental allergic asthma and acute exacerbation thereof.MethodsWild-type (WT) and IL-17RE deficient (Il-17re−/−) mice were sensitized and challenged with OVA to induce allergic airway inflammation. pIC or PBS were applied intranasally when allergic airway inflammation had been established. Pulmonary expression of inflammatory mediators, numbers of inflammatory cells, and airway hyperresponsiveness (AHR) were analyzed.ResultsAblation of IL-17RE did not affect the development of OVA-induced allergic airway inflammation and AHR. pIC induced inflammation independent of IL-17RE in the absence of allergic airway inflammation. Treatment of mice with pIC exacerbated pulmonary inflammation in sensitized and OVA-challenged mice in an IL-17RE-dependent manner. The pIC-induced expression of cytokines (e.g. keratinocyte-derived chemokine (KC), granulocyte-colony stimulating factor (G-CSF)) and recruitment of neutrophils were decreased in Il-17re−/− mice. pIC-exacerbated AHR was partially decreased in Il-17re−/− mice.ConclusionsOur results indicate that IL-17RE mediates virus-triggered exacerbations but does not have a function in the development of allergic lung disease.
Highlights
The interleukin 17 receptor E (IL-17RE) is specific for the epithelial cytokine interleukin-17C (IL-17C)
In vitro and in vivo studies showed that the expression of IL-17C in airway epithelial cells is induced by lung pathogens including rhinoviruses and that IL-17C promotes the recruitment of neutrophils into the lung [12,13,14,15,16,17,18,19,20,21,22]
Because of the functional overlap between IL-17A and IL-17C and the corresponding receptor complexes IL-17RA/IL-17RC and IL-17RA/IL-17RE, we examined the function of IL17RE in mouse models of OVA-induced experimental asthma and acute exacerbation thereof
Summary
The interleukin 17 receptor E (IL-17RE) is specific for the epithelial cytokine interleukin-17C (IL-17C). Asthma exacerbations are frequently caused by viral infections. We and others have shown that pIC induces the expression of IL-17C in airway epithelial cells. The two-hit hypothesis states that viral infections represent a second hit triggering acute asthma exacerbation in patients suffering from already established allergic lung inflammation as a first hit [3]. In vitro and in vivo studies showed that the expression of IL-17C in airway epithelial cells is induced by lung pathogens including rhinoviruses and that IL-17C promotes the recruitment of neutrophils into the lung [12,13,14,15,16,17,18,19,20,21,22]
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