Guarding the frontiers: the biology of type III interferons


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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Figure 1: Genomic organization of the type III IFNs in mice and humans.
Figure 2: Signaling pathway of type I and type III IFNs.
Figure 3: Epithelial and immune responses to viral infection in the lung.
Figure 4: Phylogenetic tree of IFN-λ based on actual or predicted protein sequences.


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We thank L. Heilesen, H.H. Gad and S. Davidson for critical reading of this manuscript and help with figures.

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Correspondence to Rune Hartmann.

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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).

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