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Ball, H. J. et al. Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice. Gene 396, 203-213

Discipline of Pathology and Bosch Institute, University of Sydney, NSW 2006, Australia.
Gene (Impact Factor: 2.08). 08/2007; 396(1):203-13. DOI: 10.1016/j.gene.2007.04.010
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ABSTRACT Indoleamine 2,3-dioxygenase (INDO) and tryptophan 2,3-dioxygenase (TDO) each catalyze the first step in the kynurenine pathway of tryptophan metabolism. We describe the discovery of another enzyme with this activity, indoleamine 2,3-dioxygenase-like protein (INDOL1), which is closely related to INDO and is expressed in mice and humans. The corresponding genes have a similar genomic structure and are situated adjacent to each other on human and mouse chromosome 8. They are likely to have arisen by gene duplication before the origin of the tetrapods. The expression of INDOL1 is highest in the mouse kidney, followed by epididymis, and liver. Expression of mouse INDOL1 was further localized to the tubular cells in the kidney and the spermatozoa. INDOL1 was assigned its name because of its structural similarity to INDO. We demonstrate that INDOL1 catalyses the conversion of tryptophan to kynurenine therefore a more appropriate nomenclature for the enzymes might be INDO-1 and INDO-2, or the more commonly-used abbreviations, IDO-1 and IDO-2. Although the two proteins have similar enzymatic activities, their different expression patterns within tissues and during malaria infection, suggests a distinct role for each protein. This identification of INDOL1 may help to explain the regulation of the diversity of physiological and patho-physiological processes in which the kynurenine pathway is involved.

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Available from: Lars S Jermiin, May 09, 2014
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    • "Indoleamine 2,3-dioxygenase-2 (IDO-like protein, INDOL1, proto-IDO) was described first in 2007 (38, 39) and has been reviewed recently (40). IDO2 has a molecular weight of 47 kDa, is composed of 420 amino acid residues, and displays 43% identity with IDO1 at the amino acid level. "
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    ABSTRACT: This review discusses the mechanisms and consequences of degradation of tryptophan (Trp) in the placenta, focusing mainly on the role of indoleamine 2,3-dioxygenase-1 (IDO1), one of three enzymes catalyzing the first step of the kynurenine pathway of Trp degradation. IDO1 has been implicated in regulation of feto-maternal tolerance in the mouse. Local depletion of Trp and/or the presence of metabolites of the kynurenine pathway mediate immunoregulation and exert antimicrobial functions. In addition to the decidual glandular epithelium, IDO1 is localized in the vascular endothelium of the villous chorion and also in the endothelium of spiral arteries of the decidua. Possible consequences of IDO1-mediated catabolism of Trp in the endothelium encompass antimicrobial activity and immunosuppression, as well as relaxation of the placental vasotonus, thereby contributing to placental perfusion and growth of both placenta and fetus. It remains to be evaluated whether other enzymes mediating Trp oxidation, such as indoleamine 2,3-dioxygenase-2, Trp 2,3-dioxygenase, and Trp hydroxylase-1 are of relevance to the biology of the placenta.
    Frontiers in Immunology 05/2014; 5:230. DOI:10.3389/fimmu.2014.00230
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    • "Although Tdo2 was originally described as a primarily hepatic enzyme, there has been increasing evidence for an involvement in the brain and brain pathophysiology (Kanai et al. 2009; van der Goot et al. 2012). Little is currently known about the role of the recently discovered enzyme Ido2 in brain (Ball et al. 2007; Yuasa et al. 2009). We investigated the expression patterns of Ido1, Ido2, and Tdo2 in two brain regions of wild-type mice using qRT-PCR (Fig. 3); the striatum, a brain region predominantly affected in HD and in YAC128 mouse model and the cerebellum, a brain region relatively spared in HD. "
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    ABSTRACT: Indoleamine 2,3 dioxygenase (Ido1), the first and rate-limiting enzyme of the kynurenine pathway (KP), is a striatally-enriched gene with increased expression levels in the YAC128 mouse model of Huntington disease (HD). Our objective in this study was to delineate age-related KP alterations in this model. Three enzymes potentially catalyze the first step of the KP; Ido1 and Indoleamine 2,3 dioxygenase-2 (Ido2) were highly expressed in the striatum and Tryptophan 2,3 dioxygenase (Tdo2) in the cerebellum. During development, Ido1 mRNA expression is dynamically regulated and chronically upregulated in YAC128 mice. Kynurenine (Kyn) to tryptophan (Trp) ratio, a measure of activity in the first step of the KP, was elevated in YAC128 striatum, but no change in Tdo2 mRNA levels or Kyn to Trp ratio was detected in the cerebellum. Ido1 induction was coincident with Trp depletion at 3 months and Kyn accumulation at 12 months of age in striatum. Changes in downstream KP metabolites of YAC128 mice generally followed a biphasic pattern with neurotoxic metabolites reduced at 3 months and increased at 12 months of age. Striatally-specfic induction of Ido1 and downstream KP alterations suggest involvement in HD pathogenesis, and should be taken into account in future therapeutic developments for HD. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 06/2013; 127(6). DOI:10.1111/jnc.12350 · 4.24 Impact Factor
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    • "In the current study we investigated the role and mechanism of IDO induction in two murine models of influenza A infection using strain PR8 and the less virulent strain X31 by monitoring IDO induction in lungs and draining LNs and evaluating the consequences of ablating IDO1 genes, one of two homologous genes (IDO1 and IDO2) that encode IDO [20], [21], on the course of host primary and recall T cell responses to influenza infection. "
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    ABSTRACT: Influenza infection stimulates protective host immune responses but paradoxically enhances lung indoleamine 2,3 dioxygenase (IDO) activity, an enzyme that suppresses helper/effector T cells and activates Foxp3-lineage regulatory CD4 T cells (Tregs). Influenza A/PR/8/34 (PR8) infection stimulated rapid elevation of IDO activity in lungs and lung-draining mediastinal lymph nodes (msLNs). Mice lacking intact IDO1 genes (IDO1-KO mice) exhibited significantly lower morbidity after sub-lethal PR8 infection, and genetic or pharmacologic IDO ablation led to much faster recovery after virus clearance. More robust influenza-specific effector CD8 T cell responses manifested in lungs of PR8-infected IDO1-KO mice, though virus clearance rates were unaffected by IDO ablation. Similar outcomes manifested in mice infected with a less virulent influenza A strain (X31). IDO induction in X31-infected lungs was dependent on IFN type II (IFNγ) signaling and was restricted to non-hematopoietic cells, while redundant IFN type 1 or type II signaling induced IDO exclusively in hematopoietic cells from msLNs. Memory T cells generated in X31-primed IDO1-KO mice protected mice from subsequent challenge with lethal doses of PR8 (100×LD50). However recall T cell responses were less robust in lung interstitial tissues, and classic dominance of TCR Vβ8.3 chain usage amongst memory CD8(+) T cells specific for influenza nucleoprotein (NP366) did not manifest in IDO1-KO mice. Thus, influenza induced IDO activity in lungs enhanced morbidity, slowed recovery, restrained effector T cell responses in lungs and shaped memory T cell repertoire generation, but did not attenuate virus clearance during primary influenza A infection.
    PLoS ONE 06/2013; 8(6):e66546. DOI:10.1371/journal.pone.0066546 · 3.23 Impact Factor
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