Interleukin 27 negatively regulates the development of interleukin 17–producing T helper cells during chronic inflammation of the central nervous system Academic Article uri icon

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.

authors

  • Stumhofer, Jason S
  • Laurence, Arian
  • Wilson, Emma H
  • Huang, Elaine
  • Tato, Cristina M
  • Johnson, Leanne M
  • Villarino, Alejandro V
  • Huang, Qiulong
  • Yoshimura, Akihiko
  • Sehy, David
  • Saris, Christiaan JM
  • O'Shea, John J
  • Hennighausen, Lothar
  • Ernst, Matthias
  • Hunter, Christopher A

publication date

  • September 2006

has subject area