Clinical relevance of indoleamine 2,3-dioxygenase for alloimmunity and transplantation

Purpose of review The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) is activated by interferon-gamma and via tryptophan depletion and the production of proapoptotic downstream metabolites IDO suppresses adaptive T-cell-mediated immunity in inflammation, host immune defence and maternal tolerance. In addition, IDO-mediated tryptophan catabolism occurring in dendritic cells is an emerging potent mechanism of peripheral tolerance. Recent findings Recent data dissecting the molecular T-cell regulatory mechanisms and immunomodulatory features of IDO have given rise to the development of new concepts for translating such naturally occurring tolerance mechanisms of IDO into the service of permanent graft acceptance, thereby eventually facilitating the ultimate goal in transplantation of donor antigen-specific unresponsiveness. Summary This review focuses on the nature and mechanisms of IDO-mediated immune regulation in alloimmunity and transplantation and outlines its clinical relevance and therapeutic implications.