Type III interferons (IFNs) or IFN-λs regulate a similar set of genes as type I IFNs, but whereas type I IFNs act globally, IFN-λs primarily target mucosal epithelial cells and protect them against the frequent viral attacks that are typical for barrier tissues. IFN-λs 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-λ4 action impairs the clearance of hepatitis C virus and could influence inflammatory responses. This constitutes a paradox that has yet to be resolved.
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We thank L. Heilesen, H.H. Gad and S. Davidson for critical reading of this manuscript and help with figures.
The authors declare no competing financial interests.
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Wack, A., Terczyńska-Dyla, E. & Hartmann, R. Guarding the frontiers: the biology of type III interferons. Nat Immunol 16, 802–809 (2015). https://doi.org/10.1038/ni.3212
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