On watching the watchers: IDO and type I/II IFN.

A series of recent studies, including an article in this issue of the European Journal of Immunology, have demonstrated that the immunoregulatory pathway of tryptophan catabolism, initiated by the enzyme indoleamine 2,3-dioxygenase (IDO), not only represents an effector mechanism of peripheral tolerance, but is also a critical participant in the promotion of an optimally protective immune response balanced between inflammation and tolerance. Although subjected to transcriptional regulation by type I/II IFN, IDO is itself required for the production of type I IFN in response to B7 signaling in CD19(+) DC. Such a bidirectional feedback loop could be part of an integrated response for preventing excessive inflammation and autoimmunity.