IL-13 suppresses double-stranded RNA-induced IFN-λ production in lung cells

Acute sthma exacerbations are frequently associated with respiratory viral infections. Although impaired production of type III IFNs (IFN-λs) is related to the severity of asthma exacerbation, the mechanisms underlying deficient IFN-λ production in asthma are poorly understood. Airway epithelial cells were stimulated in vitro with a synthetic mimetic of viral double-stranded RNA (dsRNA). IL-13, a crucial cytokine responsible for asthma pathogenesis, suppressed dsRNA-induced expression of IFN-λs, and JAK inhibitor AG490 prevented the suppression by IL-13. IL-13 per se did not affect IFN-λ production or the expressions of membrane dsRNA receptor TLR3 and of cytoplasmic receptors RIG-I and MDA5. IL-13-deficient mice exhibited more enhanced IFN-λ expression after intratracheal instillation of dsRNA than wild-type mice, whereas IFN-λ expression after dsRNA was absent in the mouse lungs of the OVA-induced asthma model. These findings suggest that IL-13 may be a putative cytokine suppressing IFN-λ production against airway viral infections in asthmatics.