Abstract
Regulation of tryptophan metabolism by indoleamine 2,3-dioxygenase (IDO) in dendritic cells (DCs) is a highly versatile modulator of immunity. In inflammation, interferon-γ is the main inducer of IDO for the prevention of hyperinflammatory responses, yet IDO is also responsible for self-tolerance effects in the longer term. Here we show that treatment of mouse plasmacytoid DCs (pDCs) with transforming growth factor-β (TGF-β) conferred regulatory effects on IDO that were mechanistically separable from its enzymic activity. We found that IDO was involved in intracellular signaling events responsible for the self-amplification and maintenance of a stably regulatory phenotype in pDCs. Thus, IDO has a tonic, nonenzymic function that contributes to TGF-β-driven tolerance in noninflammatory contexts.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptive Immunity* / drug effects
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Animals
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Dendritic Cells* / cytology
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Dendritic Cells* / drug effects
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Dendritic Cells* / enzymology
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Dendritic Cells* / immunology
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Humans
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Hypersensitivity / immunology
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Immune Tolerance* / drug effects
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Indoleamine-Pyrrole 2,3,-Dioxygenase* / immunology
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Indoleamine-Pyrrole 2,3,-Dioxygenase* / metabolism
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Signal Transduction / immunology*
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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Transforming Growth Factor beta / immunology*
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Transforming Growth Factor beta / pharmacology
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Tryptophan / metabolism
Substances
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Transforming Growth Factor beta
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Interferon-gamma
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Tryptophan