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

The Interleukin-23 receptor complex is a heterodimeric cell-surface signaling unit consisting of the IL-23 receptor (IL-23R) and the IL-12 receptor subunit beta-1 (IL-12RB1) (UniProt Q5VWK5; PubMed: 12023369). It is predominantly expressed on Th17 cells, gamma-delta T cells, and innate lymphoid cells, where it serves as the primary mediator for IL-23-induced signaling (PubMed: 24445666). Upon binding of the IL-23 cytokine, the complex recruits and activates Janus kinases (JAK2 and TYK2), leading to the phosphorylation of STAT3 and STAT4, which promotes the survival and expansion of the Th17 lineage (PubMed: 26121197). This pathway is essential for the production of pro-inflammatory cytokines such as IL-17A, IL-17F, and IL-22, which play central roles in mucosal immunity and host defense (PubMed: 21244177). Pathological overactivation of the IL-23 receptor complex is strongly linked to the pathogenesis of autoimmune and chronic inflammatory conditions, including psoriasis, Crohn's disease, and psoriatic arthritis (PubMed: 26121197). Therapeutic strategies targeting this complex include monoclonal antibodies like Guselkumab and Risankizumab that neutralize the IL-23 ligand, and emerging oral peptides like PTG-200 designed to antagonize the receptor subunits directly (ClinicalTrials.gov NCT03358758).

Other names

Interleukin-23 receptorIL-23R/IL-12RB1 complexIL23R

Inhibition of the IL-23 signaling pathway by either neutralizing the IL-23 cytokine (p19 or p40 subunits) or by directly antagonizing the IL-23 receptor complex, thereby preventing the activation of JAK2/TYK2 and downstream STAT3 phosphorylation.