Interleukin-27 pathway (IL-27 pathway)

The Interleukin-27 (IL-27) pathway is a critical immunomodulatory signaling axis composed of the heterodimeric cytokine IL-27 (subunits p28 and EBI3) and its cognate receptor complex, which consists of IL-27RA (WSX-1) and gp130 (PMID: 28344130). Upon binding, IL-27 primarily activates the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, specifically STAT1 and STAT3, to regulate the differentiation and function of various immune cells (UniProt P40189, Q8NEV9). IL-27 exhibits pleiotropic roles, acting as a pro-inflammatory agent by promoting Th1 cell differentiation and as an anti-inflammatory agent by suppressing Th17 responses and inducing the production of IL-10-producing regulatory T cells (PMID: 30108499). In the context of oncology, IL-27 is often upregulated in the tumor microenvironment where it contributes to immune evasion by inducing inhibitory receptors like PD-L1 and TIGIT on T cells, making it a high-interest target for checkpoint inhibition (PMID: 33536604). Therapeutic strategies include monoclonal antibodies like SRF388 that block IL-27 to enhance anti-tumor immunity, as well as potential applications of IL-27 agonists to treat chronic inflammatory and autoimmune diseases (ClinicalTrials.gov NCT04374877).

Other names

IL-27 signalingIL27Interleukin-27 receptor complexIL-27/IL-27R axis

Monoclonal antibodies target the IL-27 cytokine or its receptor subunits (IL-27RA/gp130) to block downstream JAK-STAT signaling, thereby reducing immunosuppression in the tumor microenvironment or modulating inflammatory responses. Recombinant IL-27 or agonists may be used to enhance its anti-inflammatory properties in autoimmune contexts.