Interleukin-23 receptor (IL-23R) (IL-23R)

The Interleukin-23 receptor (IL-23R) is a type I cytokine receptor that forms a heterodimeric signaling complex with IL-12Rβ1 to bind the IL-23 cytokine (composed of p19 and p40 subunits), initiating pro-inflammatory responses primarily through activation of the JAK/STAT pathway. This receptor features an N-terminal immunoglobulin-like domain critical for high-affinity binding to the p19 subunit of IL-23, along with cytokine receptor homology (CHR) domains that facilitate cooperative interactions, distinguishing it from gp130 despite family similarities in the IL-6/IL-12 cytokine receptor group. IL-23R plays a central role in driving T helper 17 (Th17) cell differentiation and maintenance, promoting cytokine production like IL-17 that amplifies inflammation. Dysregulation of IL-23R signaling contributes to autoimmune and inflammatory diseases such as psoriasis, psoriatic arthritis, and Crohn's disease, where elevated Th17 activity sustains chronic pathology. Therapeutically, monoclonal antibodies targeting IL-23 (e.g., risankizumab, guselkumab) or its shared p40 subunit effectively block receptor engagement, reducing disease activity with high specificity. Structural studies reveal key hotspots in the IL-23R Ig domain that restructure the cytokine for stable complex assembly, offering opportunities for selective antagonists. Unlike gp130, which homodimerizes in other complexes, IL-23R lacks a full Ig-CHR orientation for site III binding in this context, relying on distinct domain plasticity.

Other names

IL-23 receptorIL12RB2-like receptorIL-23R

Antagonism of IL-23 signaling by blocking heterodimer formation with IL-12Rβ1; Inhibition of JAK/STAT pathway activation