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

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 of IL-12 production leading to Th1 development against microbes. Expression of IL-12R is necessary for maintaining IL-12 responsiveness and controlling Th1 lineage commitment. Advances in this area have included a broader understanding of the factors involved in the regulation of the IL-12R beta 2 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)-gamma 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-gamma and subsequent activation of phagocytic cells but also plays a major role in regulating the migration and proper positioning of effector cells.