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

Nat Immunol. 2011 Jul 31;12(9):870-8. doi: 10.1038/ni.2077.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity* / drug effects
  • Animals
  • Dendritic Cells* / cytology
  • Dendritic Cells* / drug effects
  • Dendritic Cells* / enzymology
  • Dendritic Cells* / immunology
  • Humans
  • Hypersensitivity / immunology
  • Immune Tolerance* / drug effects
  • Indoleamine-Pyrrole 2,3,-Dioxygenase* / immunology
  • Indoleamine-Pyrrole 2,3,-Dioxygenase* / metabolism
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Signal Transduction / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta / pharmacology
  • Tryptophan / metabolism


  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Transforming Growth Factor beta
  • Interferon-gamma
  • Tryptophan