Meta-Biol

• Pathways

Interleukin 12 (IL-12) is heterodimeric cytokine produced by dendritic cells, macrophages and neutrophils. It is encoded by the genes Interleukin-12 subunit alpha (IL12A) and Interleukin-12 subunit beta (IL12B), which encode a 35-kDa light chain (p35) and a 40-kDa heavy chain (p40), respectively. The active IL12 heterodimer is sometimes referred to as p70. The p35 component has homology to single-chain cytokines, while p40 is homologous to the extracellular domains of members of the haematopoietic cytokine-receptor family. The IL12 heterodimer therefore resembles a cytokine linked to a soluble receptor. IL12 is involved in the differentiation of naive T cells into Th1 cells and sometimes known as T cell-stimulating factor. IL12 enhances the cytotoxic activity of Natural Killer cells and CD8+ cytotoxic T lymphocytes. IL12 also has anti-angiogenic activity, mediated by increased production of CXCL10 via interferon gamma. The IL12 receptor is a heterodimer formed by Interleukin-12 receptor subunit beta-1 (IL12RB1) and Interleukin-12 receptor subunit beta-2 (IL12RB2), both of which have extensive homology to IL6ST (gp130), the signal transducing receptor subunit of the IL6-like cytokine superfamily. IL-12RB2 is considered to play the key role in IL12 function, in part because its expression on activated T cells is stimulated by cytokines that promote Th1 cell development and inhibited by those that promote Th2 cells development. In addition, IL12 binding leads to IL12RB2 tyrosine phosphorylation, which provides binding sites for the kinases Non-receptor tyrosine-protein kinase TYK2 and Tyrosine-protein kinase JAK2. These activate transcription factor proteins in the Signal transducer and activator of transcription (STAT) family, particularly STAT4.

Cytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concentrations. Cytokines bind to specific membrane receptors, which then signal the cell via second messengers, to regulate cellular activity.

Humans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first critical hours and days of exposure to a new pathogen, our innate immune system.