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

Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells / Pallotta, Mt; Orabona, C; Volpi, C; Vacca, C; Belladonna, Ml; Bianchi, R; Servillo, G; Brunacci, C; Calvitti, M; Bicciato, Silvio; Mazza, Emilia Maria Cristina; Boon, L; Grassi, F; Fioretti, Mc; Fallarino, F; Puccetti, P; Grohmann, U.. - In: NATURE IMMUNOLOGY. - ISSN 1529-2908. - STAMPA. - 12:(2011), pp. 870-878. [10.1038/ni.2077]

Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells

BICCIATO, Silvio;MAZZA, Emilia Maria Cristina;
2011-01-01

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
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Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells / Pallotta, Mt; Orabona, C; Volpi, C; Vacca, C; Belladonna, Ml; Bianchi, R; Servillo, G; Brunacci, C; Calvitti, M; Bicciato, Silvio; Mazza, Emilia Maria Cristina; Boon, L; Grassi, F; Fioretti, Mc; Fallarino, F; Puccetti, P; Grohmann, U.. - In: NATURE IMMUNOLOGY. - ISSN 1529-2908. - STAMPA. - 12:(2011), pp. 870-878. [10.1038/ni.2077]
Pallotta, Mt; Orabona, C; Volpi, C; Vacca, C; Belladonna, Ml; Bianchi, R; Servillo, G; Brunacci, C; Calvitti, M; Bicciato, Silvio; Mazza, Emilia Maria Cristina; Boon, L; Grassi, F; Fioretti, Mc; Fallarino, F; Puccetti, P; Grohmann, U.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/673651
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