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.
Sinigaglia
F
F
francesco.sinigaglia@roche.com
D'Ambrosio
D
D
Panina-Bordignon
P
P
Rogge
L
L
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002454:Cell Differentiation; D002465:Cell Movement; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007372:Interferons / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology*; D020382:Interleukin-18 / Q000502:physiology; D018123:Receptors, Interleukin / Q000502:physiology*; D053707:Receptors, Interleukin-12; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology*
D016207:Cytokines; D020382:Interleukin-18; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D007371:Interferon-gamma; D007372:Interferons