Interleukin-12 receptor and Interleukin-23 receptor (IL-12R and IL-23R)

Interleukin-12 (IL-12) and Interleukin-23 (IL-23) are closely related, heterodimeric cytokines, sharing a p40 subunit but differing in their additional unique subunits (p35 for IL-12, p19 for IL-23)[4][5][7][10]. They are secreted mainly by antigen-presenting cells and play central but distinct roles in immune regulation. IL-12 signals through the IL-12 receptor complex (IL-12Rβ1 and IL-12Rβ2), promoting Th1 differentiation and IFN-γ production, which is crucial for defense against intracellular pathogens and tumor surveillance. IL-23 signals via the IL-23 receptor complex (IL-23R and IL-12Rβ1), inducing Th17 cell development and chronic inflammation. Their dysregulation contributes to the pathogenesis of various autoimmune, inflammatory, infectious, and neoplastic diseases. The shared p40 subunit is a validated therapeutic target; several drugs, such as ustekinumab, block both IL-12 and IL-23 pathways, while newer agents selectively target IL-23. Targeting these cytokines has transformed management of diseases like Crohn’s disease and psoriasis due to efficacy in dampening pathological inflammation without general immune suppression[2][5][8].

Other names

IL-12 (Interleukin-12)IL-23 (Interleukin-23)IL-12R (Interleukin-12 receptor)IL-23R (Interleukin-23 receptor)IL-12/23 pathwayIL-12p70 (bioactive IL-12 heterodimer)p40, p35, p19 (subunit names)

Antibody blockade of cytokine subunits: Neutralization of p40 blocks both IL-12 and IL-23-mediated signaling (e.g., ustekinumab) Selective blockade of p19: Inhibits only IL-23-mediated responses (e.g., risankizumab) Inhibition of receptor-ligand interaction: Prevents signal transduction through the respective receptor complexes