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Clin Sci (Lond). 2015 Oct;129(7):601-72. doi: 10.1042/CS20140392.

Role of indoleamine 2,3-dioxygenase in health and disease.

Author information

1
Centre for Vascular Research, Inflammation and Infection Research Group, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia Discipline of Pathology, The Charles Perkins Centre, School of Medical Sciences and Bosch Institute, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
2
Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, U.S.A.
3
Discipline of Pathology, The Charles Perkins Centre, School of Medical Sciences and Bosch Institute, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
4
Centre for Vascular Research, Inflammation and Infection Research Group, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia shane.thomas@unsw.edu.au.

Abstract

IDO1 (indoleamine 2,3-dioxygenase 1) is a member of a unique class of mammalian haem dioxygenases that catalyse the oxidative catabolism of the least-abundant essential amino acid, L-Trp (L-tryptophan), along the kynurenine pathway. Significant increases in knowledge have been recently gained with respect to understanding the fundamental biochemistry of IDO1 including its catalytic reaction mechanism, the scope of enzyme reactions it catalyses, the biochemical mechanisms controlling IDO1 expression and enzyme activity, and the discovery of enzyme inhibitors. Major advances in understanding the roles of IDO1 in physiology and disease have also been realised. IDO1 is recognised as a prominent immune regulatory enzyme capable of modulating immune cell activation status and phenotype via several molecular mechanisms including enzyme-dependent deprivation of L-Trp and its conversion into the aryl hydrocarbon receptor ligand kynurenine and other bioactive kynurenine pathway metabolites, or non-enzymatic cell signalling actions involving tyrosine phosphorylation of IDO1. Through these different modes of biochemical signalling, IDO1 regulates certain physiological functions (e.g. pregnancy) and modulates the pathogenesis and severity of diverse conditions including chronic inflammation, infectious disease, allergic and autoimmune disorders, transplantation, neuropathology and cancer. In the present review, we detail the current understanding of IDO1's catalytic actions and the biochemical mechanisms regulating IDO1 expression and activity. We also discuss the biological functions of IDO1 with a focus on the enzyme's immune-modulatory function, its medical implications in diverse pathological settings and its utility as a therapeutic target.

KEYWORDS:

3-dioxygenase; Immune cells; Immunology; Oxidative stress; cancer; immune suppression; indoleamine 2; infection; inflammation; kynurenine; tryptophan

PMID:
26186743
DOI:
10.1042/CS20140392
[Indexed for MEDLINE]

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