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Regulation of the IL‐12/IL‐12R axis: a critical step in T‐helper cell differentiation and effector function

Summary: Interleukin (IL)‐12 is required for the development of T‐helper (Th)1 cells, which have been shown to be important for protective cell‐mediated immune responses against a variety of intracellular pathogens. Recent studies have clarified the sources and the regulation ofIL‐12 production leading to Th1 development against microbes. Expression of IL‐12R is necessary for maintaining IL‐12 responsiveness and controlling Thl lineage commitment. Advances in this area have included a broader understanding of the factors involved in the regulation of the IL‐12Rβ2 signaling component. Expression of this receptor subunit in humans is critically influenced by IL‐12 and type I interferons. IL‐12 signaling results in STAT4 activation and interferon (IFN)‐γ production. Recent evidence suggests that IL‐12 also modulates a number of genes involved in leukocyte trafficking. Thus, IL‐12 is not only an important proinflammatory cytokine, which induces production of IFN‐γ and subsequent activation of phago‐cytic cells but also plays a major role in regulating the migration and proper positioning of effector cells.