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. 2021 Apr 27;17(6):349–362. doi: 10.1038/s41584-021-00606-1

Fig. 1. Type I and type III interferon signalling pathways.

Fig. 1

Type I and type III interferons can activate both Janus kinase 1 (JAK1) and non-receptor tyrosine-protein kinase TYK2 (TYK2), leading to signal transducer and activator of transcription (STAT) phosphorylation and the formation of STAT1–STAT2 heterodimers. These heterodimers can interact with interferon regulatory factor 9 (IRF9) to form the interferon stimulated gene factor 3 (ISGF3) transcription factor complex. ISGF3 translocates to the nucleus, where it can bind to interferon-stimulated regulatory element (ISRE) sequences and promote the expression of interferon-stimulated genes (ISGs). Type III interferons comparatively induce lower amplitude expression of ISGs over a longer period of time than type I interferons, possibly owing to differential negative regulation by Ubl carboxyl-terminal hydrolase 18 (USP18). Type I and type III interferons can also promote the formation of STAT1 homodimers, which upregulate IRF1 expression and lead to pro-inflammatory chemokine production. IFNλ can also signal through a variety of non-canonical mechanisms. GAS, IFNγ-activated sequence; IFN, interferon; IFNAR, IFNα receptor; IFNLR1, IFNλ receptor 1; IL-10RB, IL-10 receptor subunit-β.