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Tryptophan-2,3-Dioxygenase (TDO) deficiency is associated with subclinical neuroprotection in a mouse model of multiple sclerosis

Standard

Tryptophan-2,3-Dioxygenase (TDO) deficiency is associated with subclinical neuroprotection in a mouse model of multiple sclerosis. / Lanz, Tobias V; Williams, Sarah K; Stojic, Aleksandar; Iwantscheff, Simeon; Sonner, Jana K; Grabitz, Carl; Becker, Simon; Böhler, Laura-Inés; Mohapatra, Soumya R; Sahm, Felix; Küblbeck, Günter; Nakamura, Toshikazu; Funakoshi, Hiroshi; Opitz, Christiane A; Wick, Wolfgang; Diem, Ricarda; Platten, Michael.

In: SCI REP-UK, Vol. 7, 24.01.2017, p. 41271.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lanz, TV, Williams, SK, Stojic, A, Iwantscheff, S, Sonner, JK, Grabitz, C, Becker, S, Böhler, L-I, Mohapatra, SR, Sahm, F, Küblbeck, G, Nakamura, T, Funakoshi, H, Opitz, CA, Wick, W, Diem, R & Platten, M 2017, 'Tryptophan-2,3-Dioxygenase (TDO) deficiency is associated with subclinical neuroprotection in a mouse model of multiple sclerosis', SCI REP-UK, vol. 7, pp. 41271. https://doi.org/10.1038/srep41271

APA

Lanz, T. V., Williams, S. K., Stojic, A., Iwantscheff, S., Sonner, J. K., Grabitz, C., Becker, S., Böhler, L-I., Mohapatra, S. R., Sahm, F., Küblbeck, G., Nakamura, T., Funakoshi, H., Opitz, C. A., Wick, W., Diem, R., & Platten, M. (2017). Tryptophan-2,3-Dioxygenase (TDO) deficiency is associated with subclinical neuroprotection in a mouse model of multiple sclerosis. SCI REP-UK, 7, 41271. https://doi.org/10.1038/srep41271

Vancouver

Lanz TV, Williams SK, Stojic A, Iwantscheff S, Sonner JK, Grabitz C et al. Tryptophan-2,3-Dioxygenase (TDO) deficiency is associated with subclinical neuroprotection in a mouse model of multiple sclerosis. SCI REP-UK. 2017 Jan 24;7:41271. https://doi.org/10.1038/srep41271

Bibtex

@article{6cb5d4fb6f1f4d3581da8a3c3bf8f042,
title = "Tryptophan-2,3-Dioxygenase (TDO) deficiency is associated with subclinical neuroprotection in a mouse model of multiple sclerosis",
abstract = "The catabolism of tryptophan to immunosuppressive and neuroactive kynurenines is a key metabolic pathway regulating immune responses and neurotoxicity. The rate-limiting step is controlled by indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO). IDO is expressed in antigen presenting cells during immune reactions, hepatic TDO regulates blood homeostasis of tryptophan and neuronal TDO influences neurogenesis. While the role of IDO has been described in multiple immunological settings, little is known about TDO's effects on the immune system. TDO-deficiency is neuroprotective in C. elegans and Drosophila by increasing tryptophan and specific kynurenines. Here we have determined the role of TDO in autoimmunity and neurodegeneration in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We created reporter-TDO mice for in vivo imaging to show that hepatic but not CNS TDO expression is activated during EAE. TDO deficiency did not influence myelin-specific T cells, leukocyte infiltration into the CNS, demyelination and disease activity. TDO-deficiency protected from neuronal loss in the spinal cord but not in the optic nerves. While this protection did not translate to an improved overt clinical outcome, our data suggest that spatially distinct neuroprotection is conserved in mammals and support TDO as a potential target for treatment of diseases associated with neurodegeneration.",
keywords = "Animals, Cell Differentiation, Cell Survival, Cloning, Molecular, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental/enzymology, Genes, Reporter, Inflammation/pathology, Liver/enzymology, Lymphocyte Activation, Mice, Inbred C57BL, Mice, Transgenic, Multiple Sclerosis/enzymology, Neuroglia/metabolism, Neurons/metabolism, Neuroprotection, Phenotype, T-Lymphocytes/immunology, Tryptophan Oxygenase/deficiency",
author = "Lanz, {Tobias V} and Williams, {Sarah K} and Aleksandar Stojic and Simeon Iwantscheff and Sonner, {Jana K} and Carl Grabitz and Simon Becker and Laura-In{\'e}s B{\"o}hler and Mohapatra, {Soumya R} and Felix Sahm and G{\"u}nter K{\"u}blbeck and Toshikazu Nakamura and Hiroshi Funakoshi and Opitz, {Christiane A} and Wolfgang Wick and Ricarda Diem and Michael Platten",
year = "2017",
month = jan,
day = "24",
doi = "10.1038/srep41271",
language = "English",
volume = "7",
pages = "41271",
journal = "SCI REP-UK",
issn = "2045-2322",
publisher = "NATURE PUBLISHING GROUP",

}

RIS

TY - JOUR

T1 - Tryptophan-2,3-Dioxygenase (TDO) deficiency is associated with subclinical neuroprotection in a mouse model of multiple sclerosis

AU - Lanz, Tobias V

AU - Williams, Sarah K

AU - Stojic, Aleksandar

AU - Iwantscheff, Simeon

AU - Sonner, Jana K

AU - Grabitz, Carl

AU - Becker, Simon

AU - Böhler, Laura-Inés

AU - Mohapatra, Soumya R

AU - Sahm, Felix

AU - Küblbeck, Günter

AU - Nakamura, Toshikazu

AU - Funakoshi, Hiroshi

AU - Opitz, Christiane A

AU - Wick, Wolfgang

AU - Diem, Ricarda

AU - Platten, Michael

PY - 2017/1/24

Y1 - 2017/1/24

N2 - The catabolism of tryptophan to immunosuppressive and neuroactive kynurenines is a key metabolic pathway regulating immune responses and neurotoxicity. The rate-limiting step is controlled by indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO). IDO is expressed in antigen presenting cells during immune reactions, hepatic TDO regulates blood homeostasis of tryptophan and neuronal TDO influences neurogenesis. While the role of IDO has been described in multiple immunological settings, little is known about TDO's effects on the immune system. TDO-deficiency is neuroprotective in C. elegans and Drosophila by increasing tryptophan and specific kynurenines. Here we have determined the role of TDO in autoimmunity and neurodegeneration in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We created reporter-TDO mice for in vivo imaging to show that hepatic but not CNS TDO expression is activated during EAE. TDO deficiency did not influence myelin-specific T cells, leukocyte infiltration into the CNS, demyelination and disease activity. TDO-deficiency protected from neuronal loss in the spinal cord but not in the optic nerves. While this protection did not translate to an improved overt clinical outcome, our data suggest that spatially distinct neuroprotection is conserved in mammals and support TDO as a potential target for treatment of diseases associated with neurodegeneration.

AB - The catabolism of tryptophan to immunosuppressive and neuroactive kynurenines is a key metabolic pathway regulating immune responses and neurotoxicity. The rate-limiting step is controlled by indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO). IDO is expressed in antigen presenting cells during immune reactions, hepatic TDO regulates blood homeostasis of tryptophan and neuronal TDO influences neurogenesis. While the role of IDO has been described in multiple immunological settings, little is known about TDO's effects on the immune system. TDO-deficiency is neuroprotective in C. elegans and Drosophila by increasing tryptophan and specific kynurenines. Here we have determined the role of TDO in autoimmunity and neurodegeneration in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We created reporter-TDO mice for in vivo imaging to show that hepatic but not CNS TDO expression is activated during EAE. TDO deficiency did not influence myelin-specific T cells, leukocyte infiltration into the CNS, demyelination and disease activity. TDO-deficiency protected from neuronal loss in the spinal cord but not in the optic nerves. While this protection did not translate to an improved overt clinical outcome, our data suggest that spatially distinct neuroprotection is conserved in mammals and support TDO as a potential target for treatment of diseases associated with neurodegeneration.

KW - Animals

KW - Cell Differentiation

KW - Cell Survival

KW - Cloning, Molecular

KW - Disease Models, Animal

KW - Encephalomyelitis, Autoimmune, Experimental/enzymology

KW - Genes, Reporter

KW - Inflammation/pathology

KW - Liver/enzymology

KW - Lymphocyte Activation

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Multiple Sclerosis/enzymology

KW - Neuroglia/metabolism

KW - Neurons/metabolism

KW - Neuroprotection

KW - Phenotype

KW - T-Lymphocytes/immunology

KW - Tryptophan Oxygenase/deficiency

U2 - 10.1038/srep41271

DO - 10.1038/srep41271

M3 - SCORING: Journal article

C2 - 28117398

VL - 7

SP - 41271

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

ER -