Journal
SCIENCE
Volume 310, Issue 5749, Pages 850-855Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1117634
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Local catabolism of, the amino acid tryptophan (Trp) by indoleamine 2,3-dioxygenase ([DO) 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(H)1) cytokines. N-(3,4,-Dimethoxycinnamoyl) anthranilic acid (3,4-DAA), an orally active syntihetic 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(H)1-mediated autoimmune diseases such as MS.
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