Abstract
Interleukin 27 (IL-27) was first characterized as a proinflammatory cytokine with T helper type 1-inducing activity. However, subsequent work has demonstrated that mice deficient in IL-27 receptor (IL-27R alpha) show exacerbated inflammatory responses to a variety of challenges, suggesting that IL-27 has important immunoregulatory functions in vivo. Here we demonstrate that IL-27R alpha-deficient mice were hypersusceptible to experimental autoimmune encephalomyelitis and generated more IL-17-producing T helper cells. IL-27 acted directly on effector T cells to suppress the development of IL-17-producing T helper cells mediated by IL-6 and transforming growth factor-beta. This suppressive activity was dependent on the transcription factor STAT1 and was independent of interferon-gamma. Finally, IL-27 suppressed IL-6-mediated T cell proliferation. These data provide a mechanistic explanation for the IL-27-mediated immune suppression noted in several in vivo models of inflammation.
MeSH terms
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Animals
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Central Nervous System / immunology
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Central Nervous System / pathology
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Immune Tolerance / genetics
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Immune Tolerance / immunology
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Interferon-gamma / metabolism
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Interleukin-17 / biosynthesis*
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Interleukin-17 / genetics
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Interleukin-6 / pharmacology
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Interleukins / pharmacology
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Interleukins / physiology*
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Lymph Nodes / immunology
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Lymphocyte Activation
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Mice
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Mice, Knockout
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Receptors, Cytokine / genetics*
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Receptors, Interleukin
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STAT1 Transcription Factor / genetics
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STAT1 Transcription Factor / metabolism
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T-Lymphocytes, Helper-Inducer / drug effects
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T-Lymphocytes, Helper-Inducer / immunology*
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Transforming Growth Factor beta / pharmacology
Substances
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Il27 protein, mouse
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Il27ra protein, mouse
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Interleukin-17
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Interleukin-6
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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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Transforming Growth Factor beta
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Interferon-gamma