Interleukin-12 receptor subunit beta-1 (IL-12RB1) (IL-12RB1)

Interleukin-12 receptor subunit beta-1 (IL-12RB1) is a type I transmembrane protein that functions as a common subunit for both the IL-12 and IL-23 receptor complexes (UniProt P42701). It is primarily expressed on T cells, natural killer (NK) cells, and dendritic cells, where it specifically binds the p40 subunit shared by the cytokines IL-12 and IL-23 (NCBI Gene ID: 3594). This binding is essential for the formation of high-affinity receptor complexes that initiate the JAK-STAT signaling pathway, primarily through STAT4, which drives the differentiation of Th1 and Th17 cells and the production of interferon-gamma (PubMed: 21149606). Genetic deficiencies in IL-12RB1 are the most frequent cause of Mendelian susceptibility to mycobacterial diseases (MSMD), a condition predisposing individuals to severe infections by weakly virulent mycobacteria and Salmonella (StatPearls: NBK560519). In clinical practice, the IL-12/IL-23 axis is a major therapeutic target for autoimmune and inflammatory disorders such as psoriasis, psoriatic arthritis, and Crohn's disease. Monoclonal antibodies like ustekinumab and briakinumab modulate this pathway by binding to the p40 ligand, thereby preventing its interaction with the IL-12RB1 receptor chain and inhibiting downstream inflammatory signaling (PubMed: 30206315).

Other names

CD212IL-12 receptor beta-1 chainIL-12R-beta-1IL12RB1Interleukin-12 receptor beta-1

Inhibition of IL-12 and IL-23 signaling by preventing the binding of the shared p40 subunit to the IL-12RB1 receptor chain.