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 / M.T. Pallotta, C. Orabona, C. Volpi, C. Vacca, M.L. Belladonna, R. Bianchi, G. Servillo, C. Brunacci, M. Calvitti, S. Bicciato, E.M.C. Mazza, L. Boon, F. Grassi, M.C. Fioretti, F. Fallarino, P. Puccetti, U. Grohmann. - In: NATURE IMMUNOLOGY. - ISSN 1529-2908. - 12:9(2011), pp. 870-878. [10.1038/ni.2077]

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

F. Grassi;
2011

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.
Settore BIO/13 - Biologia Applicata
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/179634
Citazioni
  • ???jsp.display-item.citation.pmc??? 278
  • Scopus 494
  • ???jsp.display-item.citation.isi??? 482
social impact