Interleukin-27 receptor complex (IL-27R)

The Interleukin-27 (IL-27) receptor complex is a heterodimeric signaling assembly composed of the Interleukin-27 receptor subunit alpha (IL-27RA, also known as WSX-1 or TCCR) and the Interleukin-6 signal transducer (gp130 or IL6ST) [1.2.1, 1.4.1]. This complex is primarily expressed on various immune cells, including T cells, NK cells, and monocytes, where it mediates the pleiotropic effects of the cytokine IL-27 [1.2.2]. Upon ligand binding, the receptor activates the Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway, specifically signaling through STAT1 and STAT3 to regulate immune homeostasis [1.2.3, 1.4.2]. IL-27 signaling is characterized by its dual role: it can promote pro-inflammatory Th1 responses and IFN-gamma production while simultaneously exerting anti-inflammatory effects by inducing IL-10 and inhibiting Th17 cell differentiation [1.4.1, 1.5.3]. In the context of oncology, the IL-27 receptor axis is often exploited by tumors to create an immunosuppressive microenvironment, leading to the development of antagonistic antibodies like casdozokitug (SRF388) to restore anti-tumor immunity [1.3.1, 1.3.5]. Conversely, agonists of the receptor are being explored for treating autoimmune and inflammatory conditions such as inflammatory bowel disease (IBD) and rheumatoid arthritis [1.1.1, 1.1.4].

Other names

IL-27 receptorWSX-1/gp130 complexTCCR/gp130 complexInterleukin-27 receptor subunit alpha/Interleukin-6 signal transducer complex

Antagonism of the receptor complex (via ligand or receptor blockade) to inhibit immunosuppressive signaling in the tumor microenvironment; Agonism of the receptor complex to induce anti-inflammatory pathways in autoimmune and inflammatory diseases [1.1.1, 1.3.4, 1.5.3].