FIGURE 1.

Type 1 IFN signaling. Type 1 IFN signaling is mediated through several steps. (McCarty et al., 1995). Activation of endosomal TLR7/9 by viral ssDNA/RNA or endogenous nucleic acids in pDCs leads to IFN-α/β production. Activation of an important receptor, BDCA2, also promotes IFN-α/β production (Izmirly et al., 2017). In the canonical pathway, IFN-α/β binds to the IFN-α receptor (IFNAR) in IFN responsive cells (Izmirly et al., 2021). This leads to phosphorylation and activation of IFNAR associated JAKs (JAK1, Tyk2) (International Consortium for Systemic Lupus Erythematosus et al., 2008). The activated JAKs phosphorylate STAT1/STAT2, which form a heterodimer that further complexes with IRF9 in the cytoplasm (Hom et al., 2008). Finally, the STAT1-STAT2-IRF9 complex translocates to the nucleus, binds to conserved IFN-stimulated response elements (ISREs), and leads to transcription of IFN stimulated genes (ISGs).