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

Abstract

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.

• Authors: Andrew Young, Eimear Linehan, Emily Hams, Aisling C O'Hara Hall, Angela McClurg, James A Johnston, Christopher A Hunter, Padraic G Fallon, Denise C Fitzgerald
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 189 Issue 5 Pg. 2079-83 (Sep 01 2012) ISSN: 1550-6606 [Electronic] United States
• PMID: 22837488 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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