Indoleamine 2,3-dioxygenase is a Signaling Protein in Long-term Tolerance by Dendritic Cells

Overview

Journal Nat Immunol

Date 2011 Aug 2

PMID 21804557

Citations 360

Authors

Maria T Pallotta

Ciriana Orabona

Claudia Volpi

Carmine Vacca

Maria L Belladonna

Roberta Bianchi

Giuseppe Servillo

Cinzia Brunacci

Mario Calvitti

Silvio Bicciato

Emilia M C Mazza

Louis Boon

Fabio Grassi

Maria C Fioretti

Francesca Fallarino

Paolo Puccetti

Ursula Grohmann

Affiliations

Soon will be listed here.

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.

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