Abstract
IL-27 is a cytokine that regulates Th function during autoimmune and pathogen-induced immune responses. Although previous studies have shown that regulatory T cells (Tregs) express the IL-27R, and that IL-27 inhibits forkhead box P3 upregulation in vitro, little is known about how IL-27 influences Tregs in vivo. The studies presented in this article show that mice that overexpress IL-27 had decreased Treg frequencies and developed spontaneous inflammation. Although IL-27 did not cause mature Tregs to downregulate forkhead box P3, transgenic overexpression in vivo limited the size of a differentiating Treg population in a bone marrow chimera model, which correlated with reduced production of IL-2, a vital cytokine for Treg maintenance. These data identify an indirect role for IL-27 in shaping the Treg pool.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Marrow Transplantation / immunology
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Bone Marrow Transplantation / pathology
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Cells, Cultured
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Female
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Growth Inhibitors / biosynthesis
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Growth Inhibitors / genetics
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Growth Inhibitors / physiology*
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Inflammation / genetics
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Inflammation / immunology
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Inflammation / pathology
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Interleukin-2 / antagonists & inhibitors
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Interleukin-2 / biosynthesis
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Interleukins / biosynthesis
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Interleukins / genetics
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Interleukins / physiology*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Minor Histocompatibility Antigens
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Protein Subunits / biosynthesis
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Protein Subunits / genetics
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Protein Subunits / physiology*
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Radiation Chimera / immunology
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Receptors, Cytokine / biosynthesis
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Receptors, Cytokine / genetics
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Receptors, Cytokine / physiology
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism*
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T-Lymphocytes, Regulatory / pathology
Substances
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Ebi3 protein, mouse
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Growth Inhibitors
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Il27 protein, mouse
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Interleukin-2
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Interleukins
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Minor Histocompatibility Antigens
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Protein Subunits
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Receptors, Cytokine