{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T06:42:31Z","timestamp":1774334551078,"version":"3.50.1"},"reference-count":35,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5749","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2005,11,4]]},"abstract":"<jats:p>\n                    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\u20131 (T\n                    <jats:sub>H<\/jats:sub>\n                    1) cytokines.\n                    <jats:italic>N<\/jats:italic>\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\n                    <jats:sub>H<\/jats:sub>\n                    1-mediated autoimmune diseases such as MS.\n                  <\/jats:p>","DOI":"10.1126\/science.1117634","type":"journal-article","created":{"date-parts":[[2005,11,3]],"date-time":"2005-11-03T16:48:00Z","timestamp":1131036480000},"page":"850-855","source":"Crossref","is-referenced-by-count":355,"title":["Treatment of Autoimmune Neuroinflammation with a Synthetic Tryptophan Metabolite"],"prefix":"10.1126","volume":"310","author":[{"given":"Michael","family":"Platten","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Pathology (Neuropathology), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tu\u0308bingen, 72076 Tu\u0308bingen, Germany."},{"name":"Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, 1169\u2013056 Lisbon, Portugal."},{"name":"Bayhill Therapeutics Inc., Palo Alto, CA 94303, USA."}]},{"given":"Peggy P.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Pathology (Neuropathology), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tu\u0308bingen, 72076 Tu\u0308bingen, Germany."},{"name":"Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, 1169\u2013056 Lisbon, Portugal."},{"name":"Bayhill Therapeutics Inc., Palo Alto, CA 94303, USA."}]},{"given":"Sawsan","family":"Youssef","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Pathology (Neuropathology), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tu\u0308bingen, 72076 Tu\u0308bingen, Germany."},{"name":"Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, 1169\u2013056 Lisbon, Portugal."},{"name":"Bayhill Therapeutics Inc., Palo Alto, CA 94303, USA."}]},{"given":"Paulo","family":"Fontoura","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Pathology (Neuropathology), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tu\u0308bingen, 72076 Tu\u0308bingen, Germany."},{"name":"Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, 1169\u2013056 Lisbon, Portugal."},{"name":"Bayhill Therapeutics Inc., Palo Alto, CA 94303, USA."}]},{"given":"Hideki","family":"Garren","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Pathology (Neuropathology), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tu\u0308bingen, 72076 Tu\u0308bingen, Germany."},{"name":"Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, 1169\u2013056 Lisbon, Portugal."},{"name":"Bayhill Therapeutics Inc., Palo Alto, CA 94303, USA."}]},{"given":"Eun Mi","family":"Hur","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Pathology (Neuropathology), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tu\u0308bingen, 72076 Tu\u0308bingen, Germany."},{"name":"Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, 1169\u2013056 Lisbon, Portugal."},{"name":"Bayhill Therapeutics Inc., Palo Alto, CA 94303, USA."}]},{"given":"Rohit","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Pathology (Neuropathology), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tu\u0308bingen, 72076 Tu\u0308bingen, Germany."},{"name":"Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, 1169\u2013056 Lisbon, Portugal."},{"name":"Bayhill Therapeutics Inc., Palo Alto, CA 94303, USA."}]},{"given":"Lowen Y.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Pathology (Neuropathology), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tu\u0308bingen, 72076 Tu\u0308bingen, Germany."},{"name":"Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, 1169\u2013056 Lisbon, Portugal."},{"name":"Bayhill Therapeutics Inc., Palo Alto, CA 94303, USA."}]},{"given":"Brian A.","family":"Kidd","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Pathology (Neuropathology), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tu\u0308bingen, 72076 Tu\u0308bingen, Germany."},{"name":"Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, 1169\u2013056 Lisbon, Portugal."},{"name":"Bayhill Therapeutics Inc., Palo Alto, CA 94303, USA."}]},{"given":"William H.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Pathology (Neuropathology), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tu\u0308bingen, 72076 Tu\u0308bingen, Germany."},{"name":"Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, 1169\u2013056 Lisbon, Portugal."},{"name":"Bayhill Therapeutics Inc., Palo Alto, CA 94303, USA."}]},{"given":"Raymond A.","family":"Sobel","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Pathology (Neuropathology), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tu\u0308bingen, 72076 Tu\u0308bingen, Germany."},{"name":"Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, 1169\u2013056 Lisbon, Portugal."},{"name":"Bayhill Therapeutics Inc., Palo Alto, CA 94303, USA."}]},{"given":"Michael L.","family":"Selley","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Pathology (Neuropathology), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tu\u0308bingen, 72076 Tu\u0308bingen, Germany."},{"name":"Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, 1169\u2013056 Lisbon, Portugal."},{"name":"Bayhill Therapeutics Inc., Palo Alto, CA 94303, USA."}]},{"given":"Lawrence","family":"Steinman","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, CA 94305, USA."},{"name":"Department of Pathology (Neuropathology), Stanford University, Stanford, CA 94305, USA."},{"name":"Department of General Neurology and Hertie-Institute for Clinical Brain Research, University of Tu\u0308bingen, 72076 Tu\u0308bingen, Germany."},{"name":"Department of Immunology, Faculty of Medical Sciences, New University of Lisbon, 1169\u2013056 Lisbon, Portugal."},{"name":"Bayhill Therapeutics Inc., Palo Alto, CA 94303, USA."}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1457"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.5.11.1907934"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5380.1191"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(03)00072-3"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2003.11.003"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020121"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020052"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1078"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2003.10.006"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd870"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0901-762"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10145"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0305-252"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(93)90200-5"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90169-8"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/379343a0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00171-6"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01158"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8970"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099896"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/80516"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/80424"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/80525"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03727"},{"key":"e_1_3_2_26_2","unstructured":"Materials and methods are available as supporting material on Science Online."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.4.583"},{"key":"e_1_3_2_28_2","unstructured":"Data were submitted to the Gene Expression Omnibus (GEO) and can be accessed at www.ncbi.nlm.nih.gov\/geo with accession number GSE3401."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3466.1998.tb00359.x"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.091101.091806"},{"key":"e_1_3_2_31_2","unstructured":"3 4-DAA did not reduce cell viability at concentrations up to 200 \u03bcM as assessed by propidium iodine staining (fig. S2)."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071545"},{"key":"e_1_3_2_33_2","unstructured":"Treatment with 3 4-DAA was associated with a markedly suppressed lymphocytic infiltration in the spinal cords of mice with EAE (fig. S4)."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/135245850000600208"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000154520.48391.69"},{"key":"e_1_3_2_36_2","unstructured":"This work was supported by grants from the NIH the National MS Society the Phil N. Allen Trust to L.S. and funding from Angiogen Pharmaceuticals Pty. Ltd. M.P. is a recipient of an Emmy-Noether-Fellowship from the German Research Foundation (Deutsche Forschungsgemeinschaft DFG PL 315\/1-1). M.S. is a major stockholder of Angiogen Pharmaceuticals Pty. Ltd. which develops and commercializes new therapies in inflammation neurological disease and cancer. We thank M. J. Eaton and M. Britschgi for excellent technical assistance. K. Yokoyama and H. McDevitt kindly provided the MBP Ac1-11 TCR transgenic mice used for the gene microarray studies."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1117634","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:08:49Z","timestamp":1704834529000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1117634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11,4]]},"references-count":35,"journal-issue":{"issue":"5749","published-print":{"date-parts":[[2005,11,4]]}},"alternative-id":["10.1126\/science.1117634"],"URL":"https:\/\/doi.org\/10.1126\/science.1117634","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1029931.346656","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,11,4]]}}}