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

Abstract

GM-CSF is a potent pro-inflammatory cytokine that plays a pathogenic role in the CNS inflammatory disease, EAE. As IL-27 ameliorates EAE, we hypothesised 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 non-polarised and Th1 but not Th17 polarised PBMC cultures. In vivo, IL-27p28 deficiency resulted in increased GM-CSF expression by CNS infiltrating T cells during Toxoplasma gondii infection. While in vitro suppression of GM-CSF by IL-27 was independent of IL-2 suppression, IL-10 up-regulation or SOCS3 signalling, 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