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

Young A1, Linehan E, Hams E, O'Hara Hall AC, McClurg A, Johnston JA, Hunter CA, Fallon PG, Fitzgerald DC
Source: J Immunol
Publication Date: (2012)
Issue: 189 (5): 2079-83
Research Area:
Immunotherapy / Hematology
Cells used in publication:
T cell, mouse - C57BL/6
Species: mouse
Tissue Origin: blood
Culture Media:


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.