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

The interleukin-23 receptor (IL-23R) complex is a heterodimeric cell-surface signaling unit consisting of a unique IL-23R subunit and a shared IL-12 receptor beta 1 (IL-12Rβ1) subunit [UniProt Q5VWK5; Parham et al., 2002, J Immunol]. It is predominantly expressed on Th17 cells, gamma-delta T cells, and innate lymphoid cells, where it serves as the primary mediator for the pro-inflammatory cytokine IL-23 [Gaffen et al., 2014, Nat Rev Immunol]. Binding of IL-23 to this complex triggers the recruitment and activation of Janus kinases (JAK2 and TYK2), leading to the phosphorylation of STAT3 and the subsequent expression of inflammatory mediators like IL-17 and IL-22 [Teng et al., 2015, Nat Med]. This pathway is essential for the survival and effector function of Th17 cells, making it a central driver in the pathogenesis of autoimmune conditions such as psoriasis, Crohn's disease, and ulcerative colitis [Duvallet et al., 2011, Ann Med]. Therapeutic strategies targeting this complex include monoclonal antibodies that bind the IL-23 ligand (e.g., guselkumab, risankizumab) or the receptor itself, as well as emerging oral peptide inhibitors designed to block the receptor-ligand interaction [Sandborn et al., 2020, Gastroenterology]. Blocking this receptor complex effectively reduces the systemic and local inflammation associated with Th17-mediated diseases.

Other names

IL-23 receptorIL23R-IL12RB1 complexInterleukin-23 receptorIL-23R

The primary mechanism involves blocking the interaction between the IL-23 ligand and the IL-23 receptor complex, thereby preventing the activation of the JAK-STAT signaling pathway (specifically JAK2/TYK2 and STAT3) and inhibiting the production of pro-inflammatory cytokines like IL-17 and IL-22 [Gaffen et al., 2014, Nat Rev Immunol; Teng et al., 2015, Nat Med].