{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:07:41Z","timestamp":1784045261476,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,3,13]],"date-time":"2012-03-13T00:00:00Z","timestamp":1331596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:p>\n                    Vitiligo is characterized by a mostly progressive loss of the inherited skin color. The cause of the disease is still unknown, despite accumulating\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    evidence of massive oxidative stress\n                    <jats:italic>via<\/jats:italic>\n                    hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) and peroxynitrite (ONOO\n                    <jats:sup>\u2013<\/jats:sup>\n                    ) in the skin of affected individuals. The most favored hypothesis is based on autoimmune mechanisms. Since depletion of the essential amino acid L\u2010tryptophan (Trp) severely affects various immune responses, we here looked at Trp metabolism and signaling in these patients. Our\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    data revealed total absence of epidermal Trp hydroxylase activities and the presence of H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \/ONOO\n                    <jats:sup>\u2013<\/jats:sup>\n                    deactivated indoleamine 2,3\u2010dioxygenase. Aryl hydrocarbon receptor signaling is severely impaired despite the ligand (Trp dimer) being formed, as shown by mass spectrometry. Loss of this signal is supported by the absence of downstream signals (COX\u20102 and CYP1A1) as well as regulatory T\u2010lymphocytes and by computer modeling.\n                    <jats:italic>In vivo<\/jats:italic>\n                    Fourier transform Raman spectroscopy confirmed the presence of Trp metabolites together with H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    supporting deprivation of the epidermal Trp pool by Fenton chemistry. Taken together, our data support a long\u2010expressed role for\n                    <jats:italic>in loco<\/jats:italic>\n                    redox balance and a distinct immune response. These insights could open novel treatment strategies for this disease.\u2014Schallreuter, K. U., Salem, M. A. E. L., Gibbons, N. C. J., Maitland, D. J., Marsch, E., Elwary, S., Healey, A. R. Blunted epidermal L\u2010tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 2: epidermal H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \/ONOO\n                    <jats:sup>\u2013<\/jats:sup>\n                    \u2010mediated stress in vitiligo hampers indoleamine 2,3\u2010dioxygenase and aryl hydrocarbon receptor\u2010mediated immune response signaling.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 2471\u20102485 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-201897","type":"journal-article","created":{"date-parts":[[2012,3,14]],"date-time":"2012-03-14T20:18:44Z","timestamp":1331756324000},"page":"2471-2485","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Blunted epidermal L\u2010tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 2: epidermal H\n                    <sub>2<\/sub>\n                    O\n                    <sub>2<\/sub>\n                    \/ONOO\n                    <sup>\u2013<\/sup>\n                    \u2010mediated stress in vitiligo hampers indoleamine 2,3\u2010dioxygenase and aryl hydrocarbon receptor\u2010mediated immune response signaling"],"prefix":"10.1096","volume":"26","author":[{"given":"Karin U.","family":"Schallreuter","sequence":"first","affiliation":[{"name":"Institute for Pigmentary Disorders E. M. Arndt University Greifswald Germany"},{"name":"Department of Clinical and Experimental Dermatology Centre for Skin Sciences University of Bradford Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A. E. L.","family":"Salem","sequence":"additional","affiliation":[{"name":"Institute for Pigmentary Disorders E. M. Arndt University Greifswald Germany"},{"name":"Department of Clinical and Experimental Dermatology Centre for Skin Sciences University of Bradford Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick C. J.","family":"Gibbons","sequence":"additional","affiliation":[{"name":"Institute for Pigmentary Disorders E. M. Arndt University Greifswald Germany"},{"name":"Department of Clinical and Experimental Dermatology Centre for Skin Sciences University of Bradford Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek J.","family":"Maitland","sequence":"additional","affiliation":[{"name":"Department of Chemical and Forensic Sciences University of Bradford Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Marsch","sequence":"additional","affiliation":[{"name":"Institute for Pigmentary Disorders E. M. Arndt University Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souna M. A.","family":"Elwary","sequence":"additional","affiliation":[{"name":"Institute for Pigmentary Disorders E. M. Arndt University Greifswald Germany"},{"name":"Department of Clinical and Experimental Dermatology Centre for Skin Sciences University of Bradford Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Healey","sequence":"additional","affiliation":[{"name":"Analytical Centre University of Bradford Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,3,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/1074-5521(95)90090-X"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014465107"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(03)00124-8"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2079rev"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0952fje"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2007.10.007"},{"key":"e_1_2_7_8_1","article-title":"Blunted epidermal l\u2010tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 1: epidermal H2O2\/ONOO\u2013\u2010mediated stress abrogates tryptophan hydroxylase and dopa decarboxylase activities, leading to low serotonin and melatonin levels. 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