Regulation of Expression and Function of IDO in Human Dendritic Cells

In the human immune system, IDO expression and activity (IDO competence), are preferentially found in the antigenpresenting cell population, of which dendritic cells (DCs) represent an essential part. As will be comprehensively reviewed, IDO competence in human DCs, in general, is induced by molecules such as interferon-γ, which otherwise initiate immunity. IDO activity therefore, can be interpreted as a negative feedback pathway that limits uncontrolled immune responses. Because of its potent immunosuppressive effects (down-regulation of T cell responses or the expansion of T cell regulatory activity), IDO competence in human DCs is tightly regulated, at the transcriptional, translational and post-translational levels. I will critically discuss the experimental prerequisites and limits of attributing IDO competence to a mechanism of immunosuppression and examine, whether IDO competence itself can be viewed as mediating immunosuppression, or as representing one component among other immunosuppressive factors, involved in tolerogenic function of DCs. Finally, the newly emerging concepts of manipulating IDO competence as a therapy for either augmenting immune responses, such as in cancer, or down-regulating immune responses, such as in transplantation, will be summarized.