title: Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells.
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.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Pallotta
authors.forename: Ciriana
authors.initials: C
authors.lastname: Orabona
authors.forename: Claudia
authors.initials: C
authors.lastname: Volpi
authors.forename: Carmine
authors.initials: C
authors.lastname: Vacca
authors.forename: Maria L
authors.initials: ML
authors.lastname: Belladonna
authors.forename: Roberta
authors.initials: R
authors.lastname: Bianchi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Servillo
authors.forename: Cinzia
authors.initials: C
authors.lastname: Brunacci
authors.forename: Mario
authors.initials: M
authors.lastname: Calvitti
authors.forename: Silvio
authors.initials: S
authors.lastname: Bicciato
authors.forename: Emilia M C
authors.initials: EM
authors.lastname: Mazza
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Fabio
authors.initials: F
authors.lastname: Grassi
authors.forename: Maria C
authors.initials: MC
authors.lastname: Fioretti
authors.forename: Francesca
authors.initials: F
authors.lastname: Fallarino
authors.forename: Paolo
authors.initials: P
authors.lastname: Puccetti
authors.forename: Ursula
authors.initials: U
authors.lastname: Grohmann
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000494:pharmacology; D014364:Tryptophan / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D014364:Tryptophan