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 (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.
authors.affiliation: Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA. michael.platten@uni-tuebingen.de
authors.forename: Michael
authors.initials: M
authors.lastname: Platten
authors.forename: Peggy P
authors.initials: PP
authors.lastname: Ho
authors.forename: Sawsan
authors.initials: S
authors.lastname: Youssef
authors.forename: Paulo
authors.initials: P
authors.lastname: Fontoura
authors.forename: Hideki
authors.initials: H
authors.lastname: Garren
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hur
authors.forename: Rohit
authors.initials: R
authors.lastname: Gupta
authors.forename: Lowen Y
authors.initials: LY
authors.lastname: Lee
authors.forename: Brian A
authors.initials: BA
authors.lastname: Kidd
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Sobel
authors.forename: Michael L
authors.initials: ML
authors.lastname: Selley
authors.forename: Lawrence
authors.initials: L
authors.lastname: Steinman
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D001921:Brain / Q000473:pathology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D009185:Myelin Proteins / Q000276:immunology; D015398:Signal Transduction; D013116:Spinal Cord / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014364:Tryptophan / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D009185:Myelin Proteins; D062367:ortho-Aminobenzoates; D007371:Interferon-gamma; D014364:Tryptophan; C012293:tranilast