The IL-12 family of cytokines in infection, inflammation and autoimmune disorders

Inflamm Allergy Drug Targets. 2009 Mar;8(1):40-52. doi: 10.2174/187152809787582507.

Abstract

Cytokines are critical coordinators of the immune response necessary for resolving bacterial and viral assaults on the immune system. In particular, the IL-12 family of cytokines are key players in the regulation of T cell responses. These responses are orchestrated by monocytes, macrophages, and dendritic cells which produce the members of the IL-12 family of cytokines in response to infection. IL-27 and IL-23 are two cytokines that are related to IL-12; these cytokines share homology at the subunit, receptor, and signalling levels. IL-12 is composed of p35 and p40 subunits, which, when combined together form the bioactive IL-12p70. IL-23 is composed of the IL-12p40 subunit as well as the IL-23p19 subunit, which shares homology with IL-12p35. IL-27 is composed of EBI3 and p28. These three cytokines activate similar members of the JAK/STAT signalling pathways as a result of homology in their receptor components. Production of these cytokines by activated monocytes, macrophages, and dendritic cells results in the activation and differentiation of T cells. In spite of their similarity, each of these cytokines has specific roles in the regulation of immune responses. IL-12 is required for the induction of IFN-gamma production, critical for the induction of Th1 cells. IL-27 has been shown to play a role in the induction of Th1 cells from naive T cells, whereas IL-23 has been demonstrated to play a key role in the induction of the newly described Th17 cells. Recently, a novel heterodimeric and anti-inflammatory cytokine composed of the IL-12p35 and EBI3 subunits has been identified as IL-35. The biological properties of the IL-12 family of cytokines, the signalling pathways mediated by these cytokines and their role in infection, inflammation, and autoimmune diseases will be the focus of this review.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Cancer Vaccines
  • Humans
  • Immunity, Cellular
  • Infections / immunology
  • Inflammation
  • Interleukin-12 / chemistry
  • Interleukin-12 / immunology*
  • Interleukin-12 / metabolism
  • Interleukin-23 / chemistry
  • Interleukin-23 / immunology
  • Interleukin-23 / metabolism
  • Interleukins / chemistry
  • Interleukins / immunology*
  • Interleukins / metabolism
  • STAT Transcription Factors
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism*
  • Th1 Cells / pathology

Substances

  • Cancer Vaccines
  • Interleukin-23
  • Interleukins
  • MYDGF protein, human
  • STAT Transcription Factors
  • interleukin-35, human
  • Interleukin-12