학술논문
Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells.
Document Type
Article
Author
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
Source
Subject
*DENDRITIC cells
*IMMUNOREGULATION
*CELLULAR signal transduction
*DRUG tolerance
*PROTEINS
*INFLAMMATION
*INTERFERONS
*TRANSFORMING growth factors
*LABORATORY mice
*ENZYMATIC analysis
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Language
ISSN
1529-2908
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-? 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-? (TGF-?) 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-?-driven tolerance in noninflammatory contexts. [ABSTRACT FROM AUTHOR]