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-λ) 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-λ strongest action.

呼吸道病毒感染可导致肺上皮损伤、屏障功能障碍，并引发重症疾病。I型干扰素（Type I interferons, IFN-α/β）属于抗病毒细胞因子，但其临床应用因已被充分表征的多效性效应而受到限制。III型干扰素（Type III interferons, IFN-λ）的促炎活性更低，被视为更优质的治疗方案。本研究发现，在病毒感染后的康复阶段，干扰素信号通路会抑制肺上皮细胞的增殖与分化，并促进上皮细胞凋亡。这会延缓上皮修复过程，加剧疾病严重程度，并提升细菌二重感染的风险。其中IFN-α的作用最弱，IFN-β的作用处于中等水平，IFN-λ的作用最为显著。