IL12

Interleukin-12 (IL-12) is a cytokine in the IL-12 family that functions as a heterodimer consisting of two subunits, p35 and p40, encoded by IL12A and IL12B genes. In humans, the biologically active form is IL-12p70. It is primarily produced by professional antigen-presenting cells, including dendritic cells, macrophages, and monocytes, in response to microbial stimuli such as lipopolysaccharide and CpG DNA, as well as during inflammatory conditions.

IL-12 signals through a receptor composed of IL-12Rβ1 and IL-12Rβ2 subunits on natural killer cells and T lymphocytes. Receptor engagement activates the JAK-STAT signaling pathway, particularly STAT4, leading to the production of interferon-gamma (IFN-γ) by NK and T cells and promoting differentiation of naive CD4+ T cells into Th1 cells. The p40 subunit can form homodimers that can antagonize signaling, and p40 is also shared with IL-23, a related cytokine formed with a separate p19 subunit.

Biological roles of IL-12 include promoting cellular immune responses and cytotoxic activity, contributing to defense against intracellular pathogens such as certain bacteria and viruses. IL-12 can synergize with other cytokines, such as IL-18, to amplify IFN-γ production. Dysregulation of IL-12 signaling has been implicated in inflammatory and autoimmune diseases. Therapeutically, recombinant IL-12 has been explored as an immunomodulatory agent and vaccine adjuvant, though toxicity has limited widespread use. Conversely, blockade of the IL-12/IL-23 pathway by antibodies targeting the p40 subunit (for example, ustekinumab) is approved for several inflammatory diseases, reflecting the shared biology of IL-12 and IL-23 in disease pathogenesis.