Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells
Résumé
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 (IFN-γ) is the primary IDO inducer to prevent hyperinflammatory responses, yet the enzyme is also responsible for longer-term self-tolerance effects. 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 reveal that IDO is involved in intracellular signaling events responsible for self-amplification and maintenance of a stably regulatory phenotype in pDCs. Thus IDO has a tonic, non-enzymic function that contributes to TGF-β-driven tolerance in non-inflammatory contexts.
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