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

Immunol Rev. 1999 Aug;170:65-72. doi: 10.1111/j.1600-065x.1999.tb01329.x.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Cell Differentiation
  • Cell Movement
  • Cytokines / physiology
  • Disease Models, Animal
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferons / physiology
  • Interleukin-12 / physiology*
  • Interleukin-18 / physiology
  • Receptors, Interleukin / physiology*
  • Receptors, Interleukin-12
  • Signal Transduction
  • Th1 Cells / cytology*
  • Th1 Cells / immunology*

Substances

  • Cytokines
  • Interleukin-18
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • Interleukin-12
  • Interferon-gamma
  • Interferons