IL-27 is a member of the IL-12 family of cytokines. IL-27 is a heterodimer composed of the Epstein-Barr virus induced gene 3 (EBI3) subunit and p28 (also known as IL-30). EBI3 is a 34-kDa glycoprotein is homologous to the p40 subunit of IL-12 and IL-23. The p28 subunit of IL-27 is similar to p35, and has been shown to function independently of EBI3. Studies demonstrate that IL-27 binds the receptor subunit WSX-1/TCCR (also known as IL-27Ra) that associates with gp130, a common chain utilized by IL-6 family cytokines. IL-27 binding to the IL-27R that is expressed most abundantly on activated T cells and NK cells with lower expression on B cells and naïve T-cells. This leads to the phosphorylation and activation of the JAK/STAT pathway, with STAT1 and STAT3 as the predominant factors mediating the effects of IL-27. In addition to its role in mediating pro- and anti-inflammatory effects, IL-27 promotes CD4+ T cell differentiation to the TH1 lineage by inducing expression of the transcription factor T-bet and up regulating IL-12Rβ2. In doing so, IL-27 suppresses TH2 and TH17 differentiation and proliferation. IL-27 is produced by activated dendritic cells and macrophages in response to Toll-like receptor ligands and pro-inflammatory cytokines.
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