Artigo Acesso aberto Revisado por pares

Cutting Edge: Suppression of GM-CSF Expression in Murine and Human T Cells by IL-27

2012; American Association of Immunologists; Volume: 189; Issue: 5 Linguagem: Inglês

10.4049/jimmunol.1200131

ISSN

1550-6606

Autores

A. B. Young, Eimear Linehan, Emily Hams, Aisling O’Hara Hall, Angela McClurg, James A. Johnston, Christopher A. Hunter, Padraic G. Fallon, Denise Fitzgerald,

Tópico(s)

Immune Response and Inflammation

Resumo

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.

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