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 journalArticlepeer-review

333 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)850-855
Number of pages6
JournalScience
Volume310
Issue number5749
DOIs
Publication statusPublished - 4 Nov 2005

Fingerprint

Dive into the research topics of 'Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite'. Together they form a unique fingerprint.

Cite this