IL12RB2

The IL12RB2 gene encodes interleukin 12 receptor subunit beta 2 (IL-12Rβ2), also known as CDw210b. This transmembrane protein forms a functional heterodimer with IL-12Rβ1 to bind interleukin-12 (IL-12). Upon IL-12 ligation, IL-12Rβ2 triggers Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) activation, leading to STAT4 phosphorylation—key for driving Th1 cell differentiation and IFN-γ production, critical for host defense against intracellular pathogens.
Inherited IL12RB2 deficiencies cause impaired Th1 immunity, increasing susceptibility to mycobacterial (e.g., tuberculosis) and fungal infections. For drug development, modulators of the IL12/STAT4 pathway (involving IL-12Rβ2) are clinically used: ustekinumab (anti-IL12/23 p40) treats psoriasis and Crohn’s disease. Direct IL-12Rβ2 inhibitors are in preclinical stages, while activating this pathway is explored for cancer immunotherapy to enhance anti-tumor Th1 responses.