IL-27 is a heterodimeric cytokine consisting of EBV-induced gene-3 (EBI3, an IL-12 p40-related protein) and p28 (a newly discovered IL-12 P35-related protein). It is a member of the IL-6/IL-12 cytokine family and mainly produced by antigen-presenting cells, including macrophages and dendritic cells. IL-27 acts on T cells and NK cells. It has been reported that IL-27 drives rapid clonal expansion of naïve CD4+ T cells, and promotes Th1 polarization and IFN-γ production in synergy with IL-12. The IL-27-induced Th1 differentiation was mediated by rapid and marked upregulation of ICAM-1/LFA-1 interaction in a STAT1-dependent manner. IL-27 exhibits anti-inflammatory function by enhancing Th1 cell differentiation, a potent antitumor activity, through CD8+ T cell and NK cell activation. It also plays a potential therapeutic role in autoimmune disease by inhibiting Th-17 development. IL-27 mediates its biological effects through its receptor, WSX-1/T cell cytokine receptor (TCCR), which is homologous to the IL-12Rβ2 subunit. Protein gp130 serves as a functional signal-transducing molecule for IL-27.