The IL-17 receptor IL-17RE mediates polyIC-induced exacerbation of experimental allergic asthma

Abstract

Background: 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. 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. Methods: Wild-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. Results: Ablation 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-17REdependent 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. Conclusions: Our results indicate that IL-17RE mediates virus-triggered exacerbations but does not have a function in the development of allergic lung disease.

IL-17C contributes to NTHi-induced inflammation and lung damage in experimental COPD and is present in sputum during acute exacerbations

“…The pro-inflammatory cytokine IL-17C belongs to the IL-17 cytokine family and it is primary expressed by epithelial cells [3][4][5][6][7]. IL-17C shares the IL-17 receptor IL-17RA with IL-17A and regulates inflammation in an autocrine manner through the induction of cytokines, chemokines, and antimicrobial peptides [3][4][5][8][9][10]. The expression of IL-17C in airway epithelial cells is induced by microbial factors and inflammatory cytokines (e.g.…”

Multiarray screening identifies plasma proteins associated with Th17 cell differentiation and viral defense in coincident asthma and obesity

“…19,20 Studies of IL-17C in the asthma context are scarce, although recently it was found that knockout of the IL-17RE in mice led to milder virus-induced asthma exacerbations. 21 Whether IL-17C is associated with lung function, airway hyperresponsiveness, asthma control or exacerbation rate is not known.…”

“…The receptor for IL‐17C, IL‐17RE, is expressed by Th17 cells and IL‐17C activates Th17 cells to increase IL‐17A production and has been shown to recruit neutrophils to the lung 19,20 . Studies of IL‐17C in the asthma context are scarce, although recently it was found that knockout of the IL‐17RE in mice led to milder virus‐induced asthma exacerbations 21 . Whether IL‐17C is associated with lung function, airway hyperresponsiveness, asthma control or exacerbation rate is not known.…”

IL-17 Cytokines and Chronic Lung Diseases

“…Combined neutralization of both IL-13 and IL-17A diminished the pathological signs of Th2/Th17 high experimental asthma in mice [ 74 ]. Furthermore, local application of polyinosinic:polycytidylic acid (polyIC) to mice with OVA-induced experimental allergic asthma led to infiltration of IL-17A, producing natural killer (NK) cells and expression of IL-17C, which mediate exacerbation of airway inflammation, mucus hyperproduction, and AHR [ 75 , 76 ]. Since lipopolysaccharide (LPS)-induced exacerbation of experimental asthma in mice is also associated with increased release of IL-17A and can be blocked by an antibody directed against this cytokine, IL-17A could indeed play a significant role during acute asthma exacerbations triggered by bacteria as well as respiratory viruses [ 77 ].…”