Interleukin-12 and the Regulation of Innate Resistance and Adaptive Immunity

Nat Rev Immunol. 2003 Feb;3(2):133-46. doi: 10.1038/nri1001.

Abstract

Interleukin-12 (IL-12) is a heterodimeric pro-inflammatory cytokine that induces the production of interferon-gamma (IFN-gamma), favours the differentiation of T helper 1 (T(H)1) cells and forms a link between innate resistance and adaptive immunity. Dendritic cells (DCs) and phagocytes produce IL-12 in response to pathogens during infection. Production of IL-12 is dependent on differential mechanisms of regulation of expression of the genes encoding IL-12, patterns of Toll-like receptor (TLR) expression and cross-regulation between the different DC subsets, involving cytokines such as IL-10 and type I IFN. Recent data, however, argue against an absolute requirement for IL-12 for T(H)1 responses. Our understanding of the relative roles of IL-12 and other factors in T(H)1-type maturation of both CD4+ and CD8+ T cells is discussed here, including the participation in this process of IL-23 and IL-27, two recently discovered members of the new family of heterodimeric cytokines.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Cell Differentiation
  • Evolution, Molecular
  • Gene Expression Regulation
  • Humans
  • Immunity, Innate
  • Infections / immunology
  • Interleukin-12 / chemistry
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology*
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins / immunology
  • Models, Immunological
  • Molecular Structure
  • Neoplasms / immunology
  • Receptors, Interleukin / chemistry
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / immunology
  • Receptors, Interleukin-12
  • Signal Transduction
  • Th1 Cells / cytology
  • Th1 Cells / immunology

Substances

  • IL23A protein, human
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • Interleukin-12