IL27: its roles in the induction and inhibition of inflammation

Abstract

IL27 is the newest member of the IL6/IL12 family. It consists of Epstein-Barr virus-induced gene 3 (EBI3) and p28 subunits and signals through the IL27 receptor complex formed by WSX-1 and gp130 subunits. IL27-IL27 receptor interaction was initially shown to induce an early signal for the induction of Th1 responses. Recently other studies indicate that IL27 inhibits inflammatory Th17 lineage development. Despite the overall effects observed, the role of individual IL27 subunits remains controversial and is largely unclear. EBI3, while predominately found with p28 to form IL27, has different expression kinetics than p28. P28 has also been shown to signal independently of EBI3. Moreover, EBI3 has other potential binding partners such as the p35 subunit of IL12 and theoretically may regulate the inflammatory response through yet undiscovered mechanisms. Understanding the inflammatory and anti-inflammatory roles of IL27 and its subunits are essential before the immunological regulatory therapies can be developed.

Keywords: IL12; IL27; IL6; induction; inflammation; inhibition.

Figure 1

IL27 and IL27 receptor. A. IL27 is comprised of two subunits, EBI-3 and p28. EBI-3 has two fibronectin type 3 domains, and p28 has a leuicine zippper motif. B. IL27R is comprised of gp130 and IL27Rα. gp130 belongs to the IL6 receptor family. IL27Rα is also called WSX-1 or TCCR. Both chains have intracellular signaling domains.

Figure 2

IL27 promotes Th1 but inhibits Th17 cell differentiation. A. IL27 promotes näive T cells (Th0) to differentiate into Th1 effectors characterized by expression of transcription factor Tbet and IFNγ. B. IL27 inhibits CD4 T cell differentiation into Th17 effectors characterized by expression of transcription factor RORγt and IL17. This model is largely based on the results obtained from IL27Rα^−/− mice.

Figure 3

EBI3 and p28 associations other than IL27. A. EBI3 exists as a homodimer but its function is not yet known. B. EBI3 is associated with IL12p35 and is expressed during human pregnancy by syncytial trophoblasts. C. p28 has a leucine zipper motif and can homodimerize with each other.