{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:17:26Z","timestamp":1791253046064,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T00:00:00Z","timestamp":1588723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zentrales Innovationsprogramm Mittelstand","award":["ZF4257301AJ6"],"award-info":[{"award-number":["ZF4257301AJ6"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The widely varying therapeutic response of patients with inflammatory bowel disease (IBD) continues to raise questions regarding the unclarified heterogeneity of pathological mechanisms promoting disease progression. While biomarkers for the differentiation of Crohn\u2019s disease (CD) versus ulcerative colitis (UC) have been suggested, specific markers for a CD subclassification in ileal CD versus colonic CD are still rare. Since an altered signature of the tryptophan metabolism is associated with chronic inflammatory disease, we sought to characterize potential biomarkers by focusing on the downstream enzymes and metabolites of kynurenine metabolism. Using immunohistochemical stainings, we analyzed and compared the mucosal tryptophan immune metabolism in bioptic samples from patients with active inflammation due to UC or CD versus healthy controls. Localization-specific quantification of immune cell infiltration, tryptophan-metabolizing enzyme expression and mucosal tryptophan downstream metabolite levels was performed. We found generally increased immune cell infiltrates in the tissue of all patients with IBD. However, in patients with CD, significant differences were found between regulatory T cell and neutrophil granulocyte infiltration in the ileum compared with the colon. Furthermore, we observed decreased kynurenine levels as well as strong kynureninase (KYNU) expression specifically in patients with ileal CD. Correspondingly, significantly elevated levels of the kynurenine metabolite 3-hydroxyanthranilic acid were detected in the ileal CD samples. Highlighting the heterogeneity of the different phenotypes of CD, we identified KYNU as a potential mucosal biomarker allowing the localization-specific differentiation of ileal CD versus colonic CD.<\/jats:p>","DOI":"10.3390\/jcm9051360","type":"journal-article","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T04:46:07Z","timestamp":1588826767000},"page":"1360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Inflammation-Induced Mucosal KYNU Expression Identifies Human Ileal Crohn\u2019s Disease"],"prefix":"10.3390","volume":"9","author":[{"given":"Meik","family":"Huhn","sequence":"first","affiliation":[{"name":"Goethe Universit\u00e4t, pharmazentrum frankfurt\/ZAFES, Institute of Pharmacology and Toxicology, Hospital of the Goethe University, 60590 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Herrero San Juan","sequence":"additional","affiliation":[{"name":"Goethe Universit\u00e4t, pharmazentrum frankfurt\/ZAFES, Institute of Pharmacology and Toxicology, Hospital of the Goethe University, 60590 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balint","family":"Melcher","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Klinikum Bayreuth, 95445 Bayreuth, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Dreis","sequence":"additional","affiliation":[{"name":"Goethe Universit\u00e4t, pharmazentrum frankfurt\/ZAFES, Institute of Pharmacology and Toxicology, Hospital of the Goethe University, 60590 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin G.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Goethe Universit\u00e4t, pharmazentrum frankfurt\/ZAFES, Institute of Pharmacology and Toxicology, Hospital of the Goethe University, 60590 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Schwiebs","sequence":"additional","affiliation":[{"name":"Goethe Universit\u00e4t, pharmazentrum frankfurt\/ZAFES, Institute of Pharmacology and Toxicology, Hospital of the Goethe University, 60590 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Collins","sequence":"additional","affiliation":[{"name":"Interdisciplinary Crohn-Colitis Center Rhein-Main, Schifferstrasse 59, 60594 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef M.","family":"Pfeilschifter","sequence":"additional","affiliation":[{"name":"Goethe Universit\u00e4t, pharmazentrum frankfurt\/ZAFES, Institute of Pharmacology and Toxicology, Hospital of the Goethe University, 60590 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Vieth","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Klinikum Bayreuth, 95445 Bayreuth, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3558-3341","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Stein","sequence":"additional","affiliation":[{"name":"Interdisciplinary Crohn-Colitis Center Rhein-Main, Schifferstrasse 59, 60594 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4499-2510","authenticated-orcid":false,"given":"Heinfried H.","family":"Radeke","sequence":"additional","affiliation":[{"name":"Goethe Universit\u00e4t, pharmazentrum frankfurt\/ZAFES, Institute of Pharmacology and Toxicology, Hospital of the Goethe University, 60590 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2634","DOI":"10.1016\/j.cgh.2019.04.040","article-title":"Should We Divide Crohn\u2019s Disease Into Ileum-Dominant and Isolated Colonic Diseases?","volume":"17","author":"Dulai","year":"2019","journal-title":"Clin. 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