Abstract
Regulatory T cells (Tregs) are committed to suppressive functions. Recently, it was proposed that Tregs could produce IL-17 under proinflammatory, polarizing conditions. We studied the role of Tregs on IL-17 production in the absence of exogenous cytokines and insults. Using in vitro and in vivo approaches, we determined that under neutral conditions, simultaneous activation of Tregs and naive CD4(+) conventional T cells in the presence of APCs resulted in conversion of Tregs into IL-17-producing cells, and endogenous IL-1β was mandatory in this process. Mechanistic analysis revealed that the IL-1R1 was highly expressed on Tregs and that IL-1β induced marked activation of p38 and JNK, which were involved in IL-17 production. These observations could have important implications on therapeutic strategies using Tregs.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antigen Presentation / immunology
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Antigen-Presenting Cells / immunology
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Cell Differentiation / immunology*
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Cell Separation
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Coculture Techniques
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Interleukin-17 / biosynthesis*
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Interleukin-17 / immunology
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Interleukin-1beta / immunology*
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Interleukin-1beta / metabolism
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Lymphocyte Activation / immunology*
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MAP Kinase Kinase 4 / immunology
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Mice
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Mice, Inbred C57BL
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Signal Transduction / immunology
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology
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T-Lymphocytes, Regulatory / cytology*
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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p38 Mitogen-Activated Protein Kinases / immunology
Substances
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Interleukin-17
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Interleukin-1beta
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4