Interferons disrupt lung epithelial repair during recovery from respiratory infection [RN19197]

Respiratory viral infections cause lung epithelial damage, barrier dysfunction and severe disease. Type I interferons (IFN-a/b) are antiviral cytokines whose therapeutic use is limited by well-characterized pleiotropic effects. Type III IFNs (IFN-?) are less pro-inflammatory and regarded a superior treatment option. Here, we show that IFN signalling reduces lung epithelial proliferation and differentiation and increases epithelial apoptosis during recovery from viral infection. This delays epithelial repair, increasing disease severity and the risk of bacterial superinfection. IFN-a has least effects, with IFN-b intermediate and IFN-? strongest action. Overall design: C57BL/6 (WT) or IFNLR deficient mice were infected or not with influenza, and at XXX time point, epithelial cells (MARKERS) were FACS sorted and lysed into RNA buffer, The indicated number of biological repeats was performed.