Molecules in focus: indoleamine 2,3-dioxygenase.
Indoleamine 2,3-dioxygenase (IDO) is a heme enzyme that initiates the oxidative degradation of the least abundant, essential amino acid, l-tryptophan, along the kynurenine pathway. The local cellular depletion of l-tryptophan that results may enable the host to inhibit the growth of various infectious pathogens in vivo. However, over the past decade, it has become increasingly apparent that IDO also represents an important immune control enzyme. Thus, cells expressing IDO, seemingly paradoxically, are capable of suppressing local T cell responses to promote immune tolerance under various physiological and pathophysiological conditions of medical importance, including infectious diseases, foetal rejection, organ transplantation, neuropathology, inflammatory and auto-immune disorders and cancer. In this review, we briefly outline the biochemical properties of IDO, its known and hypothetical functions and the medical implications for inhibition or induction of IDO and/or its downstream catabolites in health and disease.
King
Nicholas J C
NJ
Department of Pathology, Bosch Institute, School of Medical Sciences, University of Sydney, Sydney, Australia. nickk@pathology.usyd.edu.au
Thomas
Shane R
SR
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007113:Immunity, Innate / Q000502:physiology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007371:Interferon-gamma / Q000502:physiology; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D014364:Tryptophan