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Cutting edge: suppression of GM-CSF expression in murine and human T cells by IL-27.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2012 Sep 01; Vol. 189 (5), pp. 2079-83. Date of Electronic Publication: 2012 Jul 25. - Publication Year :
- 2012
-
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.
- Subjects :
- Animals
Cell Polarity genetics
Cell Polarity immunology
Cells, Cultured
Granulocyte-Macrophage Colony-Stimulating Factor genetics
Humans
Inflammation Mediators pharmacology
Inflammation Mediators physiology
Interleukin-17 pharmacology
Lymphocyte Activation genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
T-Lymphocyte Subsets metabolism
T-Lymphocyte Subsets pathology
Toxoplasmosis immunology
Toxoplasmosis pathology
Granulocyte-Macrophage Colony-Stimulating Factor antagonists & inhibitors
Granulocyte-Macrophage Colony-Stimulating Factor biosynthesis
Immune Tolerance genetics
Interleukin-17 physiology
T-Lymphocyte Subsets immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 189
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 22837488
- Full Text :
- https://doi.org/10.4049/jimmunol.1200131