title: 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: Centre for Infection and Immunity, Queen's University Belfast, Belfast BT9 7AE, Northern Ireland.
authors: Andrew
authors: A
authors: Young
authors: Eimear
authors: E
authors: Linehan
authors: Emily
authors: E
authors: Hams
authors: Aisling C
authors: AC
authors: O'Hara Hall
authors: Angela
authors: A
authors: McClurg
authors: James A
authors: JA
authors: Johnston
authors: Christopher A
authors: CA
authors: Hunter
authors: Padraic G
authors: PG
authors: Fallon
authors: Denise C
authors: DC
authors: Fitzgerald
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D018836:Inflammation Mediators / Q000494:pharmacology / Q000502:physiology; D020381:Interleukin-17 / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014123:Toxoplasmosis / Q000276:immunology / Q000473:pathology
chemical_list: D018836:Inflammation Mediators; D020381:Interleukin-17; D016178:Granulocyte-Macrophage Colony-Stimulating Factor