Interleukin 27 Negatively Regulates the Development of Interleukin 17-producing T Helper Cells During Chronic Inflammation of the Central Nervous System

Nat Immunol. 2006 Sep;7(9):937-45. doi: 10.1038/ni1376. Epub 2006 Aug 13.

Abstract

Studies have focused on the events that influence the development of interleukin 17 (IL-17)-producing T helper cells (T(H)-17 cells) associated with autoimmunity, such as experimental autoimmune encephalitis, but relatively little is known about the cytokines that antagonize T(H)-17 cell effector responses. Here we show that IL-27 receptor-deficient mice chronically infected with Toxoplasma gondii developed severe neuroinflammation that was CD4+ T cell dependent and was associated with a prominent IL-17 response. In vitro, treatment of naive primary T cells with IL-27 suppressed the development T(H)-17 cells induced by IL-6 and transforming growth factor-beta, which was dependent on the intracellular signaling molecule STAT1 but was independent of inhibition of IL-6 signaling mediated by the suppressor protein SOCS3. Thus IL-27, a potent inhibitor of T(H)-17 cell development, may be a useful target for treating inflammatory diseases mediated by these cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / analysis
  • Central Nervous System / immunology
  • Central Nervous System / parasitology
  • Encephalitis / immunology
  • Encephalitis / parasitology
  • Encephalitis / pathology
  • Interleukin-17 / analysis*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukins / genetics
  • Interleukins / pharmacology
  • Interleukins / physiology*
  • Lymphocyte Activation* / genetics
  • Mice
  • Mice, Knockout
  • Receptors, Cytokine / drug effects
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / metabolism
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Toxoplasma*
  • Toxoplasmosis, Cerebral / immunology*
  • Toxoplasmosis, Cerebral / pathology

Substances

  • CD4 Antigens
  • Il27 protein, mouse
  • Il27ra protein, mouse
  • Interleukin-17
  • Interleukin-6
  • Interleukins
  • Receptors, Cytokine
  • STAT1 Transcription Factor
  • Socs3 protein, mouse
  • Stat1 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins