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IL-27 is a heterodimeric cytokine from the IL-12 family, encoded by the EBI3 and IL-27p28 genes. Expressed by antigen-presenting cells, it interacts with the IL-27 receptor (IL-27R). IL-27 has both pro- and anti-inflammatory roles, regulating T-helper cell development, suppressing T-cell proliferation, stimulating cytotoxic T-cell activity, and inducing B-cell isotype switching.
It drives the rapid expansion of naive CD4 T-cells, promoting TH1 differentiation while inhibiting TH2 and TH17 cell development. IL-27 activates various signaling pathways, including STAT1, STAT3, and p38 MAPK, and enhances interferon-gamma production in naive CD4 T-cells when combined with IL-12. It also suppresses pro-inflammatory cytokines like IL-2 and IL-6, and its antitumor and antiangiogenic activities involve increasing antiangiogenic chemokines. Additionally, IL-27 has antiviral properties, inhibiting HIV-1 replication.