Guarding the frontiers: the biology of type III interferons

Type III interferons (IFNs) or IFN-lambda s regulate a similar set of genes as type I IFNs, but whereas type I IFNs act globally, IFN-lambda s primarily target mucosal epithelial cells and protect them against the frequent viral attacks that are typical for barrier tissues. IFN-lambda s thereby help to maintain healthy mucosal surfaces through immune protection, without the significant immune-related pathogenic risk associated with type I IFN responses. Type III IFNs also target the human liver, with dual effects: they induce an antiviral state in hepatocytes, but specific IFN-lambda 4 action impairs the clearance of hepatitis C virus and could influence inflammatory responses. This constitutes a paradox that has yet to be resolved.