Associates with EBI3 to form the IL-27 interleukin, a heterodimeric cytokine which functions in innate immunity. IL-27 has pro- and anti-inflammatory properties, that can regulate T-helper cell development, suppress T-cell proliferation, stimulate cytotoxic T-cell activity, induce isotype switching in B-cells, and that has diverse effects on innate immune cells. Among its target cells are CD4 T-helper cells which can differentiate in type 1 effector cells (TH1), type 2 effector cells (TH2) and IL17 producing helper T-cells (TH17). It drives rapid clonal expansion of naive but not memory CD4 T-cells. It also strongly synergizes with IL-12 to trigger interferon-gamma/IFN-gamma production of naive CD4 T-cells, binds to the cytokine receptor WSX-1/TCCR which appears to be required but not sufficient for IL-27-mediated signal transduction. IL-27 potentiate the early phase of TH1 response and suppress TH2 and TH17 differentiation. It induces the differentiation of TH1 cells via two distinct pathways, p38 MAPK/TBX21- and ICAM1/ITGAL/ERK-dependent pathways. It also induces STAT1, STAT3, STAT4 and STAT5 phosphorylation and activates TBX21/T-Bet via STAT1 with resulting IL12RB2 up-regulation, an event crucial to TH1 cell commitment. It suppresses the expression of GATA3, the inhibitor TH1 cells development. In CD8 T-cells, it activates STATs as well as GZMB. IL-27 reveals to be a potent inhibitor of TH17 cell development and of IL-17 production. Indeed IL27 alone is also able to inhibit the production of IL17 by CD4 and CD8 T-cells. While IL-27 suppressed the development of pro-inflammatory Th17 cells via STAT1, it inhibits the development of anti-inflammatory inducible regulatory T-cells, iTreg, independently of STAT1. IL-27 has also an effect on cytokine production, it suppresses pro-inflammatory cytokine production such as IL2, IL4, IL5 and IL6 and activates suppressors of cytokine signaling such as SOCS1 and SOCS3. Apart from suppression of cytokine production, IL-27 also antagonizes the effects of some cytokines such as IL6 through direct effects on T-cells. Another important role of IL-27 is its antitumor activity as well as its antiangiogenic activity with activation of production of antiangiogenic chemokines such as IP-10/CXCL10 and MIG/CXCL9. Heterodimer with EBI3; not disulfide-linked. This heterodimer is known as interleukin IL-27. Poorly secreted without coexpression of EBI3. Expressed in macrophages and dendritic cells. By LPS and Interferon gamma in primary astrocytes and microglia. Induced by Toll-like receptor ligand in dendritic cells. Inhibited by PPAR-alpha agonist such as fenofibrate and produced by TNF-alpha in microglia. O-glycosylated. In mouse models of experimental autoimmune encephalitis (EAE) induced by Toxoplasma Gondi infection, brain levels of IL-27 are massively increased. Deficiency of IL-27 receptors in this mouse model with EAE induces development of a more severe neuroinflammation than in wild-type mice with EAE. This excessive neuroinflammation is associated with increased numbers of TH17 cells in the central nervous system (CNS). Continuous administration of IL-27 to EAE mice produces a strong suppressive effect on active EAE, with reduced CNS infiltration of TH17 cells and TH17 cells activity. Mice injected with B16F10 tumor cells develop tumors and lung metastasis. In mice injected with B16F10 tumor cells stably transfected with IL-27, tumor cells grow much more slowly and the number of pulmonary metastasis is markedly reduced. IL-27 exhibits a strong antitumor activity as well as antiangiogenic activity with massive decreased of microvessels density in lung metastasis. Similarly, mice injected with C26 colon tumor cells transfected with IL-27 acquire tumor-specific protective activity and exhibit minimal tumor growth with enhanced IFN-gamma production. This antitumor activity is abolished in TBX21-deficient mice. Neuroblastoma cells overexpressing IL-27 also demonstrate markedly delayed growth; This tumor regression appears to be dependent on CD8 cells. Belongs to the IL-6 superfamily.