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.
|Titolo:||Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
|Data di pubblicazione:||2011|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/ni.2077|
|Appare nelle tipologie:||01 - Articolo su periodico|