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Inflammation-Induced Mucosal KYNU Expression Identifies Human Ileal Crohn’s Disease

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’s disease (CD) versus ulcerative...

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Autores principales: Huhn, Meik, Herrero San Juan, Martina, Melcher, Balint, Dreis, Caroline, Schmidt, Katrin G., Schwiebs, Anja, Collins, Janet, Pfeilschifter, Josef M., Vieth, Michael, Stein, Jürgen, Radeke, Heinfried H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290775/
https://www.ncbi.nlm.nih.gov/pubmed/32384670
http://dx.doi.org/10.3390/jcm9051360
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author Huhn, Meik
Herrero San Juan, Martina
Melcher, Balint
Dreis, Caroline
Schmidt, Katrin G.
Schwiebs, Anja
Collins, Janet
Pfeilschifter, Josef M.
Vieth, Michael
Stein, Jürgen
Radeke, Heinfried H.
author_facet Huhn, Meik
Herrero San Juan, Martina
Melcher, Balint
Dreis, Caroline
Schmidt, Katrin G.
Schwiebs, Anja
Collins, Janet
Pfeilschifter, Josef M.
Vieth, Michael
Stein, Jürgen
Radeke, Heinfried H.
author_sort Huhn, Meik
collection PubMed
description 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’s 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.
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spelling pubmed-72907752020-06-17 Inflammation-Induced Mucosal KYNU Expression Identifies Human Ileal Crohn’s Disease Huhn, Meik Herrero San Juan, Martina Melcher, Balint Dreis, Caroline Schmidt, Katrin G. Schwiebs, Anja Collins, Janet Pfeilschifter, Josef M. Vieth, Michael Stein, Jürgen Radeke, Heinfried H. J Clin Med Article 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’s 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. MDPI 2020-05-06 /pmc/articles/PMC7290775/ /pubmed/32384670 http://dx.doi.org/10.3390/jcm9051360 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huhn, Meik
Herrero San Juan, Martina
Melcher, Balint
Dreis, Caroline
Schmidt, Katrin G.
Schwiebs, Anja
Collins, Janet
Pfeilschifter, Josef M.
Vieth, Michael
Stein, Jürgen
Radeke, Heinfried H.
Inflammation-Induced Mucosal KYNU Expression Identifies Human Ileal Crohn’s Disease
title Inflammation-Induced Mucosal KYNU Expression Identifies Human Ileal Crohn’s Disease
title_full Inflammation-Induced Mucosal KYNU Expression Identifies Human Ileal Crohn’s Disease
title_fullStr Inflammation-Induced Mucosal KYNU Expression Identifies Human Ileal Crohn’s Disease
title_full_unstemmed Inflammation-Induced Mucosal KYNU Expression Identifies Human Ileal Crohn’s Disease
title_short Inflammation-Induced Mucosal KYNU Expression Identifies Human Ileal Crohn’s Disease
title_sort inflammation-induced mucosal kynu expression identifies human ileal crohn’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290775/
https://www.ncbi.nlm.nih.gov/pubmed/32384670
http://dx.doi.org/10.3390/jcm9051360
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