Interleukin 27 receptor subunit alpha (IL27RA) (IL27RA)

Interleukin 27 receptor subunit alpha (IL27RA), also known as WSX-1 or TCCR, is a type I cytokine receptor that forms a functional heterodimeric complex with glycoprotein 130 (gp130) to mediate signaling for the cytokine IL-27. Upon binding its ligand, IL27RA triggers the activation of the JAK-STAT pathway, specifically involving STAT1 and STAT3, which plays a pivotal role in regulating both innate and adaptive immune responses. Biologically, it is essential for the early differentiation of Th1 cells and the suppression of pro-inflammatory Th17 and Th2 cell lineages, while also inducing the production of the anti-inflammatory cytokine IL-10. In the context of disease, IL27RA signaling acts as an immune checkpoint in the tumor microenvironment, where its activation can suppress anti-tumor immunity, making it a target for antagonist antibodies like casdozokitug (SRF388) in cancers such as hepatocellular carcinoma. Conversely, its role in limiting excessive inflammation makes it a potential target for agonistic approaches in autoimmune disorders and sepsis. Therapeutic strategies currently focus on modulating this axis to either enhance immune surveillance in oncology or restore immune homeostasis in chronic inflammatory conditions.

Other names

WSX-1TCCRCRL1ZcytoR1IL-27R-alphaT-cell cytokine receptor type 1Cytokine receptor-like 1Type I T-cell cytokine receptor

Antagonism of the IL-27/IL-27RA interaction to modulate immune responses, particularly to enhance anti-tumor immunity or suppress excessive inflammation.