Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells

Nat Immunol. 2006 Sep;7(9):929-36. doi: 10.1038/ni1375. Epub 2006 Aug 13.


Interleukin 27 (IL-27) was first characterized as a proinflammatory cytokine with T helper type 1-inducing activity. However, subsequent work has demonstrated that mice deficient in IL-27 receptor (IL-27R alpha) show exacerbated inflammatory responses to a variety of challenges, suggesting that IL-27 has important immunoregulatory functions in vivo. Here we demonstrate that IL-27R alpha-deficient mice were hypersusceptible to experimental autoimmune encephalomyelitis and generated more IL-17-producing T helper cells. IL-27 acted directly on effector T cells to suppress the development of IL-17-producing T helper cells mediated by IL-6 and transforming growth factor-beta. This suppressive activity was dependent on the transcription factor STAT1 and was independent of interferon-gamma. Finally, IL-27 suppressed IL-6-mediated T cell proliferation. These data provide a mechanistic explanation for the IL-27-mediated immune suppression noted in several in vivo models of inflammation.

MeSH terms

  • Animals
  • Central Nervous System / immunology
  • Central Nervous System / pathology
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Immune Tolerance / genetics
  • Immune Tolerance / immunology
  • Interferon-gamma / metabolism
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics
  • Interleukin-6 / pharmacology
  • Interleukins / pharmacology
  • Interleukins / physiology*
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Receptors, Cytokine / genetics*
  • Receptors, Interleukin
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Transforming Growth Factor beta / pharmacology


  • Il27 protein, mouse
  • Il27ra protein, mouse
  • Interleukin-17
  • Interleukin-6
  • Interleukins
  • Receptors, Cytokine
  • Receptors, Interleukin
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Transforming Growth Factor beta
  • Interferon-gamma