Cutting Edge: Suppression of GM-CSF Expression in Murine and Human T Cells by IL-27: suppression of GM-CSF expression in murine and human T cells by IL-27

Andrew Young, Eimear Linehan, Emily Hams, Aisling C. O'Hara Hall, Angela McClurg, James A. Johnston, Christopher A. Hunter, Padraig G. Fallon, Denise C. Fitzgerald

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)2079-2083
Number of pages5
JournalJournal of Immunology
Volume189
Issue number5
Early online date25 Jul 2012
DOIs
Publication statusPublished - 01 Sep 2012

ASJC Scopus subject areas

  • Immunology

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