Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite

Michael Platten; Peggy P. Ho; Sawsan Youssef; Paulo Fontoura; Hideki Garren; Eun Mi Hur; Rohit Gupta; Lowen Y. Lee; Brian A. Kidd; William H. Robinson; Raymond A. Sobel; Michael L. Selley; Lawrence Steinman

doi:10.1126/science.1117634

Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite

Michael Platten, Peggy P. Ho, Sawsan Youssef, Paulo Fontoura, Hideki Garren, Eun Mi Hur, Rohit Gupta, Lowen Y. Lee, Brian A. Kidd, William H. Robinson, Raymond A. Sobel, Michael L. Selley, Lawrence Steinman

Research output: Contribution to journal › Article › peer-review

368 Scopus citations

Abstract

Local catabolism of the amino acid tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. We show that IDO transcription was increased when myelin-specific T cells were stimulated with tolerogenic altered self-peptides. Catabolites of Trp suppressed proliferation of myelin-specific T cells and inhibited production of proinflammatory T helper-1 (T_H1) cytokines. N-(3,4,- Dimethoxycinnamoyl) anthranilic acid (3,4-DAA), an orally active synthetic derivative of the Trp metabolite anthranilic acid, reversed paralysis in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis (MS). Trp catabolites and their derivatives offer a new strategy for treating T_H1-mediated autoimmune diseases such as MS.

Original language	English
Pages (from-to)	850-855
Number of pages	6
Journal	Science
Volume	310
Issue number	5749
DOIs	https://doi.org/10.1126/science.1117634
State	Published - 4 Nov 2005
Externally published	Yes

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title = "Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite",

abstract = "Local catabolism of the amino acid tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. We show that IDO transcription was increased when myelin-specific T cells were stimulated with tolerogenic altered self-peptides. Catabolites of Trp suppressed proliferation of myelin-specific T cells and inhibited production of proinflammatory T helper-1 (TH1) cytokines. N-(3,4,- Dimethoxycinnamoyl) anthranilic acid (3,4-DAA), an orally active synthetic derivative of the Trp metabolite anthranilic acid, reversed paralysis in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis (MS). Trp catabolites and their derivatives offer a new strategy for treating TH1-mediated autoimmune diseases such as MS.",

author = "Michael Platten and Ho, {Peggy P.} and Sawsan Youssef and Paulo Fontoura and Hideki Garren and Hur, {Eun Mi} and Rohit Gupta and Lee, {Lowen Y.} and Kidd, {Brian A.} and Robinson, {William H.} and Sobel, {Raymond A.} and Selley, {Michael L.} and Lawrence Steinman",

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doi = "10.1126/science.1117634",

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T1 - Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite

AU - Platten, Michael

AU - Ho, Peggy P.

AU - Youssef, Sawsan

AU - Fontoura, Paulo

AU - Garren, Hideki

AU - Hur, Eun Mi

AU - Gupta, Rohit

AU - Lee, Lowen Y.

AU - Kidd, Brian A.

AU - Robinson, William H.

AU - Sobel, Raymond A.

AU - Selley, Michael L.

AU - Steinman, Lawrence

PY - 2005/11/4

Y1 - 2005/11/4

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AB - Local catabolism of the amino acid tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. We show that IDO transcription was increased when myelin-specific T cells were stimulated with tolerogenic altered self-peptides. Catabolites of Trp suppressed proliferation of myelin-specific T cells and inhibited production of proinflammatory T helper-1 (TH1) cytokines. N-(3,4,- Dimethoxycinnamoyl) anthranilic acid (3,4-DAA), an orally active synthetic derivative of the Trp metabolite anthranilic acid, reversed paralysis in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis (MS). Trp catabolites and their derivatives offer a new strategy for treating TH1-mediated autoimmune diseases such as MS.

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Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite

Abstract

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