Indoleamine 2,3-dioxygenase and regulatory function: tryptophan starvation and beyond.

Indoleamine 2,3-dioxygenase (IDO) is an ancestral enzyme that, initially confined to the regulation of tryptophan availability in local tissue microenvironments, is now considered to play a wider role that extends to homeostasis and plasticity of the immune system. Thus, IDO biology has many implications for many aspects of immunopathology, including viral infections, neoplasia, autoimmunity, and chronic inflammation. Its immunoregulatory effects are mainly mediated by dendritic cells (DCs) and involve not only tryptophan deprivation but also production of kynurenines that act on IDO(-) DCs--thus rendering an otherwise stimulatory DC capable of regulatory effects--as well as on T cells. As a result, IDO(+) DCs mediate multiple effects on T lymphocytes, including inhibition of proliferation, apoptosis, and differentiation toward a regulatory phenotype.