Interferon Axis — Type I & Type II Signalling
Two interferon families, one kinase pair, and completely different biology. Type I interferons — IFN-α and IFN-β, made after cGAS–STING or TLR sensing drives IRF3 and IRF7 — signal through IFNAR1/IFNAR2 to TYK2 and JAK1, and assemble the three-part ISGF3 complex (STAT1, STAT2, IRF9) on ISRE elements. That switches on the antiviral programme: PKR, OAS1, MX1, IFIT1, ISG15, viperin and tetherin. Type II interferon — IFN-γ, from NK and Th1 cells — uses the same STAT1 but pairs it with itself through IFN-γR1, JAK1 and JAK2, reading GAS elements instead and inducing IRF1: MHC upregulation, the CXCL9/CXCL10/CXCL11 axis that recruits CXCR3+ T cells — and, in the same breath, PD-L1 and IDO1. USP18, SOCS1 and SOCS3 close both arms down. Click any protein for the matching Assay Genie In Vivo antibody or ELISA kit.
The same STAT1, two different complexes. This is the detail that makes the interferon system confusing until you see it drawn. Type I interferon builds ISGF3 — STAT1 plus STAT2 plus the DNA-binding subunit IRF9 — and that trimer reads ISRE elements. Type II interferon builds a STAT1 homodimer (the gamma-activated factor, GAF) and reads GAS elements. One transcription factor subunit, two complexes, two promoter grammars, two largely non-overlapping gene sets. It also explains why a STAT1 phospho-blot alone cannot tell you which interferon a cell is responding to, and why STAT1 deficiency compromises antiviral and antimycobacterial defence at once.
The induction step is where the other maps in this library connect. Cytosolic DNA runs through cGAS and STING to IRF3; endosomal dsRNA and CpG DNA run through TLR3 and TLR9 to IRF3 and IRF7. IRF3 gives the first wave, dominated by IFN-β; IRF7, itself an interferon-stimulated gene, drives the amplification wave of IFN-α subtypes. That feed-forward loop is why type I interferon responses are sharp and self-amplifying, and why they need equally sharp brakes. IFN-λ (type III) uses its own receptor but converges on the same ISGF3, which is why it produces an antiviral state largely restricted to epithelium.
IFN-γ is the immunological interferon, and it cuts both ways. Through IRF1 it raises MHC class I and class II — making a tumour or graft more visible — and induces CXCL9, CXCL10 and CXCL11, the three ligands that pull CXCR3+ effector T cells into tissue. The same signal induces PD-L1 and IDO1. That is adaptive resistance: the interferon a successful T-cell response produces is also the signal that installs the brake it will later run into. If you are reading a PD-L1 stain, you are partly reading a local IFN-γ measurement, which is why CXCL9 and CXCL10 often track response better than PD-L1 itself.
The brakes are not interchangeable. USP18 binds IFNAR2 and displaces JAK1 — a receptor-level block specific to the type I arm, and the reason chronic type I signalling desensitises. SOCS1 and SOCS3 act on the kinases themselves and are induced by both arms. Sustained, unresolved type I signalling with failing brakes is the "interferon signature" of lupus and the interferonopathies; too little is failure of antiviral defence. The In Vivo tie-in: the range covers IFN-α, IFN-β, IFN-γ (clones XMG1.2 and H22), the receptors IFNAR-1 and CD119, plus CXCL9, CXCR3, PD-L1 and MHC class I — enough to block either arm at ligand or receptor level and read the consequence downstream. JAK/STAT and cGAS–STING each have their own dedicated map in this library; they appear here as entry nodes rather than being redrawn. For research use only; not for use in diagnostic or therapeutic procedures.
Every protein node links to a product — In Vivo antibody, ELISA kit or research antibody.