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Immunological Relevance of the Coevolution of IDO1 and AHR.

Jaronen M, Quintana FJ - Front Immunol (2014)

Bottom Line: Indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) are considered rate-limiting enzymes in the tryptophan catabolism and play important roles in the regulation of the immunity.Moreover, AHR and IDO/TDO are closely interconnected: AHR regulates IDO and TDO expression, and kynurenine produced by IDO/TDO is an AHR agonist.In this review, we propose to examine the relationship between AHR and IDO/TDO and its relevance for the regulation of the immune response in health and disease.

View Article: PubMed Central - PubMed

Affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School , Boston, MA , USA.

ABSTRACT
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified because of its role in controlling the cellular response to environmental molecules. More recently, AHR has been shown to play a crucial role in controlling innate and adaptive immune responses through several mechanisms, one of which is the regulation of tryptophan metabolism. Indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) are considered rate-limiting enzymes in the tryptophan catabolism and play important roles in the regulation of the immunity. Moreover, AHR and IDO/TDO are closely interconnected: AHR regulates IDO and TDO expression, and kynurenine produced by IDO/TDO is an AHR agonist. In this review, we propose to examine the relationship between AHR and IDO/TDO and its relevance for the regulation of the immune response in health and disease.

No MeSH data available.


Schematic representation of the kynurenine pathway in human beings (mammal), C. elegans, and D. melanogaster. Pathway tree demonstrates differences between mammalian and invertebrate tryptophan catabolism. Mammalian enzymes are depicted in black, C. elegans enzymes in blue, and D. melanogaster in red. Modified from Ref. (89)
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Figure 2: Schematic representation of the kynurenine pathway in human beings (mammal), C. elegans, and D. melanogaster. Pathway tree demonstrates differences between mammalian and invertebrate tryptophan catabolism. Mammalian enzymes are depicted in black, C. elegans enzymes in blue, and D. melanogaster in red. Modified from Ref. (89)

Mentions: Additional putative kynurenine pathway related genes have been identified in the C. elegans genome (89) (Figure 2). The knock down of tdo-2, for example, abrogated the gut granule fluorescence (90, 91). Involvement of the C. elegans kynurenine pathway has been demonstrated in neurodegeneration and aging: in a C. elegans model of Parkinson’s disease; RNAi knock down of tdo-2 reduced α-synuclein aggregation-induced toxicity and increased life span (92). However, these effects were proven to be a result of increased tryptophan rather than changed levels of kynurenines (92).


Immunological Relevance of the Coevolution of IDO1 and AHR.

Jaronen M, Quintana FJ - Front Immunol (2014)

Schematic representation of the kynurenine pathway in human beings (mammal), C. elegans, and D. melanogaster. Pathway tree demonstrates differences between mammalian and invertebrate tryptophan catabolism. Mammalian enzymes are depicted in black, C. elegans enzymes in blue, and D. melanogaster in red. Modified from Ref. (89)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202789&req=5

Figure 2: Schematic representation of the kynurenine pathway in human beings (mammal), C. elegans, and D. melanogaster. Pathway tree demonstrates differences between mammalian and invertebrate tryptophan catabolism. Mammalian enzymes are depicted in black, C. elegans enzymes in blue, and D. melanogaster in red. Modified from Ref. (89)
Mentions: Additional putative kynurenine pathway related genes have been identified in the C. elegans genome (89) (Figure 2). The knock down of tdo-2, for example, abrogated the gut granule fluorescence (90, 91). Involvement of the C. elegans kynurenine pathway has been demonstrated in neurodegeneration and aging: in a C. elegans model of Parkinson’s disease; RNAi knock down of tdo-2 reduced α-synuclein aggregation-induced toxicity and increased life span (92). However, these effects were proven to be a result of increased tryptophan rather than changed levels of kynurenines (92).

Bottom Line: Indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) are considered rate-limiting enzymes in the tryptophan catabolism and play important roles in the regulation of the immunity.Moreover, AHR and IDO/TDO are closely interconnected: AHR regulates IDO and TDO expression, and kynurenine produced by IDO/TDO is an AHR agonist.In this review, we propose to examine the relationship between AHR and IDO/TDO and its relevance for the regulation of the immune response in health and disease.

View Article: PubMed Central - PubMed

Affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School , Boston, MA , USA.

ABSTRACT
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified because of its role in controlling the cellular response to environmental molecules. More recently, AHR has been shown to play a crucial role in controlling innate and adaptive immune responses through several mechanisms, one of which is the regulation of tryptophan metabolism. Indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO) are considered rate-limiting enzymes in the tryptophan catabolism and play important roles in the regulation of the immunity. Moreover, AHR and IDO/TDO are closely interconnected: AHR regulates IDO and TDO expression, and kynurenine produced by IDO/TDO is an AHR agonist. In this review, we propose to examine the relationship between AHR and IDO/TDO and its relevance for the regulation of the immune response in health and disease.

No MeSH data available.