Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4

Immunol Rev. 2004 Dec;202:139-56. doi: 10.1111/j.0105-2896.2004.00211.x.


Produced in response to a variety of pathogenic organisms, interleukin (IL)-12 and IL-23 are key immunoregulatory cytokines that coordinate innate and adaptive immune responses. These dimeric cytokines share a subunit, designated p40, and bind to a common receptor chain, IL-12R beta 1. The receptor for IL-12 is composed of IL-12R beta 1 and IL-12R beta 2, whereas IL-23 binds to a receptor composed of IL-12R beta 1 and IL-23R. Both cytokines activate the Janus kinases Tyk2 and Jak2, the transcription factor signal transducer and activator of transcription 4 (STAT4), as well as other STATs. A major action of IL-12 is to promote the differentiation of naive CD4+ T cells into T-helper (Th) 1 cells, which produce interferon (IFN)-gamma, and deficiency of IL-12, IL-12R subunits or STAT4 is similar in many respects. In contrast, IL-23 promotes end-stage inflammation. Targeting IL-12, IL-23, and their downstream signaling elements would therefore be logical strategies for the treatment of immune-mediated diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / physiology*
  • Humans
  • Interleukin-12 / deficiency
  • Interleukin-12 / physiology*
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins / deficiency
  • Interleukins / physiology*
  • Receptors, Interleukin / physiology
  • Receptors, Interleukin-12
  • STAT4 Transcription Factor
  • Signal Transduction / immunology
  • Signal Transduction / physiology*
  • Trans-Activators / chemistry
  • Trans-Activators / deficiency
  • Trans-Activators / immunology
  • Trans-Activators / physiology*


  • DNA-Binding Proteins
  • IL23A protein, human
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • Trans-Activators
  • Interleukin-12