Skip to main content
. 2020 Aug 7;11:1573. doi: 10.3389/fimmu.2020.01573

Figure 1.

Figure 1

Transcriptional Control of IL-27 Synthesis. Antigen experienced immune cells (APCs, DCs, and macrophages) act as sources of IL-27. Various cellular receptors such as Toll-Like Receptors (TLR4), IL-1βR, and CD40 promote IL-27 synthesis. The expression of IL-27 subunits from APCs can be induced using TLR agonists Poly(I:C), lipopolysaccharide (LPS), and CpG-DNA, for TLR3, TLR4, and TLR9, respectively. (A) The expression of the IL27p28 subunit can be induced through signals coming from the TLR4/MyD88/AP-1/c-Fos signaling axis. (B) Other signaling axes that culminate in the induction of IL-27p28 synthesis are- TLR3/TLR4-TRIF-IRF3/IRF7; IFN-γ/MyD88/IRF8 and IFN-α/IFN-β-STAT1/STAT2-IRF1/IRF9. (C) IFN-γ can induce IL-27 expression via stimulating JNK, MAPKs, and PI3K signaling. (D) EBI3 expression is induced by signaling through TLR2/TLR4/TLR9-MyD88-NF-κB/PU.1. (E) Both p50 and p65 can bind to the EBI3 promoter. (F) Exogenous stimuli from IL-1βR or CD40-CD154 ligation can also trigger IL-27 synthesis in a MyD88 dependent fashion. Besides NF-κB, c-Rel, recruitment of PU.1, and IRF1 and IRF3 are essential events that regulate IL-27 synthesis by shaping its transcriptional landscape. Both IFN-γ, along with IFN-α and IFN-β are reported to be associated with p28 expression in DCs.