Description: IL-27, a member of the IL-12 family, is a heterodimeric protein consisting of the p40-related protein Epstein-Barr virus-induced gene 3 (EBI3) non-covalently linked to an IL-12p35-related protein, p28 (also known as IL-30). IL-27 is produced by activated APCs and mature dendritic cells. IL-27 exerts its activities on NK cells and naïve CD4+ T cells; mRNA expression analysis of IL-27 receptor components (WSX-1/TCCR and gp130) suggests that IL-27 may also target other cells, including mast cells and monocytes. Binding of IL-27 to WSX-1/gp130 activates JAK1, STAT1, and STAT3 and STAT1/3 phosphorylation. WSX-1/TCCR-deficient mice develop impaired Th1 responses and are more susceptible to infection with L. monocytogenes suggesting that Th1 responses require IL-27. Although activation of WSX-1 is required for the initiation of Th1 responses, it is not necessary for maintaining Th1 responses. IL-27 alone is not able to induce the differentiation of CD4+ T cells into IFN-γ-producing cells, suggesting a role for IL-27 as an initial activator of Th1 responses. An important effect of IL-27 in initiating Th1 responses is the induction of the Th1-specific transcription factor T-bet as well as the suppression of the Th2-specific transcription factor GATA-3. T-bet plays a critical role in Th1 differentiation by its ability to maintain IL-12Rβ2 expression following CD4+ T cell activation.
Recent studies indicate that IL-27 has a potent antitumor activity. In vitro, IL-27 has been found to act directly on naïve CD8 cells, generating CTL with enhanced granzyme B expression. In vivo, IL-27 has been reported to augment CTL activity, inhibit tumor growth, and induce complete regression of primary and metastatic neuroblastoma tumors.
