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(H)1) 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(H)1-mediated autoimmune diseases such as MS.
Publication types
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
MeSH terms
- Adoptive Transfer
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
- Antigen-Presenting Cells / drug effects
- Antigen-Presenting Cells / immunology
- Brain / pathology
- Cell Line
- Cytokines / biosynthesis
- Disease Models, Animal
- Encephalomyelitis, Autoimmune, Experimental / drug therapy*
- Encephalomyelitis, Autoimmune, Experimental / immunology
- Female
- Histocompatibility Antigens Class II / immunology
- Histocompatibility Antigens Class II / metabolism
- Immune Tolerance
- Immunosuppressive Agents / pharmacology
- Immunosuppressive Agents / therapeutic use
- Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
- Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
- Interferon-gamma / immunology
- Lymphocyte Activation
- Mice
- Mice, Transgenic
- Microglia / drug effects
- Microglia / immunology
- Multiple Sclerosis / drug therapy
- Multiple Sclerosis / immunology
- Multiple Sclerosis / pathology
- Myelin Proteins / immunology
- Signal Transduction
- Spinal Cord / pathology
- T-Lymphocytes / immunology
- Th1 Cells / immunology
- Th2 Cells / immunology
- Tryptophan / metabolism*
- ortho-Aminobenzoates / administration & dosage
- ortho-Aminobenzoates / pharmacology
- ortho-Aminobenzoates / therapeutic use*
Substances
- Anti-Inflammatory Agents, Non-Steroidal
- Cytokines
- Histocompatibility Antigens Class II
- Immunosuppressive Agents
- Indoleamine-Pyrrole 2,3,-Dioxygenase
- Myelin Proteins
- ortho-Aminobenzoates
- Interferon-gamma
- Tryptophan
- tranilast