IL-27 is a heterodimeric cytokine that consists of EBI3, an IL-12p40-related protein, and p28, an IL-12p35-related polypeptide. IL-27 can be allocated to the IL-6/IL-12 superfamily of cytokines which include also IL-23. This family is defined based on similarities in the structural motifs of the ligands, such as a common four-helix bundle, their receptors, which contain a hematopoietin receptor domain. IL-27 signaling occurs via a receptor complex composed of the signal transducing receptor chains WSX-1 and glycoprotein (gp) 130. Whereas WSX-1 is the IL-27–specific receptor chain, gp130 is the common receptor subunit of IL-6 type cytokines. IL-27 signaling in na?ve CD4+ T cells leads to activation and phosphorylation of STAT1 and STAT3.