Divergent effects of IL-12 and IL-23 on the production of IL-17 by human T cells

Eur J Immunol. 2006 Mar;36(3):661-70. doi: 10.1002/eji.200535239.


IL-23 is regarded as a major pro-inflammatory mediator in autoimmune disease, a role which until recently was ascribed to its related cytokine IL-12. IL-23, an IL-12p40/p19 heterodimeric protein, binds to IL-12Rbeta1/IL-23R receptor complexes. Mice deficient for p19, p40 or IL-12Rbeta1 are resistant to experimental autoimmune encephalomyelitis or collagen-induced arthritis. Paradoxically, however, IL-12Rbeta2- and IL-12p35-deficient mice show remarkable increases in disease susceptibility, suggesting divergent roles of IL-23 and IL-12 in modulating inflammatory processes. IL-23 induces IL-17, which mediates inflammation and tissue remodeling, but the role of IL-12 in this respect remains unidentified. We investigated the roles of exogenous (recombinant) and endogenous (macrophage-derived) IL-12 and IL-23, on IL-17-induction in human T-cells. IL-23 enhanced IL-17 secretion, as did IL-2, IL-15, IL-18 and IL-21. In contrast, IL-12 mediated specific inhibition of IL-17 production. These data support the role of IL-23 in inflammation through stimulating IL-17 production by T lymphocytes, and importantly indicate a novel regulatory function for IL-12 by specifically suppressing IL-17 secretion. These data therefore extend previous reports that had indicated unique functions for IL-23 and IL-12 due to distinct receptor expression and signal transduction complexes, and provide novel insights into the regulation of immunity, inflammation and immunopathology.

MeSH terms

  • Animals
  • Arthritis / chemically induced
  • Arthritis / immunology
  • Cells, Cultured
  • Collagen / administration & dosage
  • Collagen / adverse effects
  • Collagen / immunology
  • Cytokines / pharmacology
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Interleukin-12 / deficiency
  • Interleukin-12 / immunology*
  • Interleukin-12 / pharmacology
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins / deficiency
  • Interleukins / immunology*
  • Interleukins / pharmacology
  • Mice
  • Mice, Knockout
  • Receptors, Interleukin / immunology
  • Receptors, Interleukin-12
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*


  • Cytokines
  • IL23A protein, human
  • Il23a protein, mouse
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • Interleukin-12
  • Collagen