Abstract
The cytokine IL-27 is important for restricting inflammation in response to a wide variety of immune challenges. In this study, we demonstrate that IL-27 induces expression of the anti-inflammatory cytokine IL-10 by CD4+ and CD8+ T cells. IL-27 relied upon the Th1 transcription factor STAT1 to induce IL-10+IFN-gamma+FoxP3- Th1 cells, which were recently shown to be key negative regulators during certain infections. Il27ra-/- mice generated fewer IL-10+ T cells during both Listeria monocytogenes infection and experimental autoimmune encephalomyelitis. The data presented here indicate a novel mechanism for the induction of IL-10 expression by T cells and provide a mechanistic basis for the suppressive effects of IL-27.
MeSH terms
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Adjuvants, Immunologic / physiology
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Animals
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism*
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism*
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Cells, Cultured
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Forkhead Transcription Factors* / metabolism
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Inflammation Mediators / antagonists & inhibitors
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Inflammation Mediators / metabolism
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Inflammation Mediators / physiology
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Interferon-gamma / biosynthesis
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Interleukin-10 / antagonists & inhibitors
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Interleukin-10 / biosynthesis*
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Interleukin-10 / deficiency
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Interleukin-10 / genetics
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Interleukins / metabolism
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Interleukins / physiology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Receptors, Cytokine / deficiency
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Receptors, Cytokine / genetics
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Receptors, Interleukin
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STAT1 Transcription Factor / physiology
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Adjuvants, Immunologic
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Il27 protein, mouse
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Il27ra protein, mouse
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Inflammation Mediators
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Interleukins
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Receptors, Cytokine
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Receptors, Interleukin
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STAT1 Transcription Factor
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Stat1 protein, mouse
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Interleukin-10
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Interferon-gamma