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Pallotta, Maria T; Orabona, Ciriana; Volpi, Claudia; Vacca, Carmine; Belladonna, Maria L; Bianchi, Roberta; Servillo, Giuseppe; Brunacci, Cinzia; Calvitti, Mario; Bicciato, Silvio; Mazza, Emilia M C; Boon, Louis; Grassi, Fabio; Fioretti, Maria C; Fallarino, Francesca; Puccetti, Paolo; Grohmann, Ursula
Nature immunology, 09/2011, Volume: 12, Issue: 9Journal Article
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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