IDO: A double-edged sword for TH1/TH2 regulation

Indoleamine 2,3-dioxygenase (IDO) has been well defined as one of the important immunosuppressive properties for TH1 cell-mediated immune responses, but its function in TH2 dominant system is poorly understood. Recently, an appreciable number of publications suggest that the role of IDO in TH2 cell regulation may be different from that of TH1 immune responses. Here we review the evidence on the regulatory function of IDO and tryptophan metabolites in TH1/TH2 differentiation. We propose that IDO-kynurenine pathway can serve as a negative feedback loop for TH1 cells but it may play a distinct role in up-regulating TH2 dominant immune responses.