Cutting edge: suppression of GM-CSF expression in murine and human T cells by IL-27

J Immunol. 2012 Sep 1;189(5):2079-83. doi: 10.4049/jimmunol.1200131. Epub 2012 Jul 25.


GM-CSF is a potent proinflammatory cytokine that plays a pathogenic role in the CNS inflammatory disease experimental autoimmune encephalomyelitis. As IL-27 alleviates experimental autoimmune encephalomyelitis, we hypothesized that IL-27 suppresses GM-CSF expression by T cells. We found that IL-27 suppressed GM-CSF expression in CD4+ and CD8+ T cells in splenocyte and purified T cell cultures. IL-27 suppressed GM-CSF in Th1, but not Th17, cells. IL-27 also suppressed GM-CSF expression by human T cells in nonpolarized and Th1- but not Th17-polarized PBMC cultures. In vivo, IL-27p28 deficiency resulted in increased GM-CSF expression by CNS-infiltrating T cells during Toxoplasma gondii infection. Although in vitro suppression of GM-CSF by IL-27 was independent of IL-2 suppression, IL-10 upregulation, or SOCS3 signaling, we observed that IL-27-driven suppression of GM-CSF was STAT1 dependent. Our findings demonstrate that IL-27 is a robust negative regulator of GM-CSF expression in T cells, which likely inhibits T cell pathogenicity in CNS inflammation.

Publication types

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

MeSH terms

  • Animals
  • Cell Polarity / genetics
  • Cell Polarity / immunology
  • Cells, Cultured
  • Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Humans
  • Immune Tolerance* / genetics
  • Inflammation Mediators / pharmacology
  • Inflammation Mediators / physiology
  • Interleukin-17 / pharmacology
  • Interleukin-17 / physiology*
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology
  • Toxoplasmosis / immunology
  • Toxoplasmosis / pathology


  • Inflammation Mediators
  • Interleukin-17
  • Granulocyte-Macrophage Colony-Stimulating Factor