Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system

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

Research output: Contribution to journalArticlepeer-review

723 Citations (Scopus)

Abstract

Studies have focused on the events that influence the development of interleukin 17 (IL-17)-producing T helper cells (TH-17 cells) associated with autoimmunity, such as experimental autoimmune encephalitis, but relatively little is known about the cytokines that antagonize TH-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 TH-17 cells induced by IL-6 and transforming growth factor-β, 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 TH-17 cell development, may be a useful target for treating inflammatory diseases mediated by these cells.

Original languageEnglish
Pages (from-to)937-945
Number of pages9
JournalNature Immunology
Volume7
Issue number9
DOIs
Publication statusPublished - 2006 Sep
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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