Effects of Epithelial IL-13Rα2 Expression in Inflammatory Bowel Disease
Background: Mucosal IL-13 Receptor alpha 2 (IL13RA2) mRNA expression is one of the best predictive markers for primary non-responsiveness to infliximab therapy in patients with inflammatory bowel disease (IBD). The objective of this study was to understand how IL-13Rα2, a negative regulator of IL-13...
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Frontiers Media S.A.
2018-12-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02983/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bram Verstockt Bram Verstockt Clémentine Perrier Clémentine Perrier Gert De Hertogh Jonathan Cremer Jonathan Cremer Brecht Creyns Brecht Creyns Gert Van Assche Gert Van Assche Marc Ferrante Marc Ferrante Jan L. Ceuppens Séverine Vermeire Séverine Vermeire Christine Breynaert |
spellingShingle |
Bram Verstockt Bram Verstockt Clémentine Perrier Clémentine Perrier Gert De Hertogh Jonathan Cremer Jonathan Cremer Brecht Creyns Brecht Creyns Gert Van Assche Gert Van Assche Marc Ferrante Marc Ferrante Jan L. Ceuppens Séverine Vermeire Séverine Vermeire Christine Breynaert Effects of Epithelial IL-13Rα2 Expression in Inflammatory Bowel Disease Frontiers in Immunology IL13RA2 goblet cells anti-TNF non-responsiveness IBD inflammatory bowel disease infliximab |
author_facet |
Bram Verstockt Bram Verstockt Clémentine Perrier Clémentine Perrier Gert De Hertogh Jonathan Cremer Jonathan Cremer Brecht Creyns Brecht Creyns Gert Van Assche Gert Van Assche Marc Ferrante Marc Ferrante Jan L. Ceuppens Séverine Vermeire Séverine Vermeire Christine Breynaert |
author_sort |
Bram Verstockt |
title |
Effects of Epithelial IL-13Rα2 Expression in Inflammatory Bowel Disease |
title_short |
Effects of Epithelial IL-13Rα2 Expression in Inflammatory Bowel Disease |
title_full |
Effects of Epithelial IL-13Rα2 Expression in Inflammatory Bowel Disease |
title_fullStr |
Effects of Epithelial IL-13Rα2 Expression in Inflammatory Bowel Disease |
title_full_unstemmed |
Effects of Epithelial IL-13Rα2 Expression in Inflammatory Bowel Disease |
title_sort |
effects of epithelial il-13rα2 expression in inflammatory bowel disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-12-01 |
description |
Background: Mucosal IL-13 Receptor alpha 2 (IL13RA2) mRNA expression is one of the best predictive markers for primary non-responsiveness to infliximab therapy in patients with inflammatory bowel disease (IBD). The objective of this study was to understand how IL-13Rα2, a negative regulator of IL-13 signaling, can contribute to IBD pathology.Methods:IL13RA2 knockout (KO) and wild type (WT) mice were exposed to dextran sodium sulfate (DSS) in drinking water to induce colitis. Furthermore, mucosal biopsies and resection specimen of healthy individuals and IBD patients before the start of anti-tumor necrosis factor (anti-TNF) therapy were obtained for immunohistochemistry and gene expression analysis.Results: After induction of DSS colitis, IL13RA2 KO mice had similar disease severity, but recovered more rapidly than WT animals. Goblet cell numbers and mucosal architecture were also more rapidly restored in IL13RA2 KO mice. In mucosal biopsies of active IBD patients, immunohistochemistry revealed that IL-13Rα2 protein was highly expressed in epithelial cells, while expression was restricted to goblet cells in healthy controls. Mucosal IL13RA2 mRNA negatively correlated with mRNA of several goblet cell-specific and barrier genes, and with goblet cell numbers.Conclusions: The data suggest that IL-13Rα2 on epithelial cells contributes to IBD pathology by negatively influencing goblet cell recovery, goblet cell function and epithelial restoration after injury. Therefore, blocking IL-13Rα2 could be a promising target for restoration of the epithelial barrier in IBD. |
topic |
IL13RA2 goblet cells anti-TNF non-responsiveness IBD inflammatory bowel disease infliximab |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.02983/full |
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doaj-d9d49cafa599439a8d6fd6e6d6a1a9492020-11-25T00:40:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-12-01910.3389/fimmu.2018.02983432447Effects of Epithelial IL-13Rα2 Expression in Inflammatory Bowel DiseaseBram Verstockt0Bram Verstockt1Clémentine Perrier2Clémentine Perrier3Gert De Hertogh4Jonathan Cremer5Jonathan Cremer6Brecht Creyns7Brecht Creyns8Gert Van Assche9Gert Van Assche10Marc Ferrante11Marc Ferrante12Jan L. Ceuppens13Séverine Vermeire14Séverine Vermeire15Christine Breynaert16KU Leuven, Department of Chronic Diseases, Metabolism and Ageing, Translational Research for Gastrointestinal Disorders, Leuven, BelgiumUniversity Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, BelgiumKU Leuven, Department of Chronic Diseases, Metabolism and Ageing, Translational Research for Gastrointestinal Disorders, Leuven, BelgiumKU Leuven, Laboratory of Clinical Immunology, Department of Microbiology and Immunology, Leuven, BelgiumKU Leuven, Department of Imaging & Pathology, Translational Cell & Tissue Research, Leuven, BelgiumKU Leuven, Department of Chronic Diseases, Metabolism and Ageing, Translational Research for Gastrointestinal Disorders, Leuven, BelgiumKU Leuven, Laboratory of Clinical Immunology, Department of Microbiology and Immunology, Leuven, BelgiumKU Leuven, Department of Chronic Diseases, Metabolism and Ageing, Translational Research for Gastrointestinal Disorders, Leuven, BelgiumKU Leuven, Laboratory of Clinical Immunology, Department of Microbiology and Immunology, Leuven, BelgiumKU Leuven, Department of Chronic Diseases, Metabolism and Ageing, Translational Research for Gastrointestinal Disorders, Leuven, BelgiumUniversity Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, BelgiumKU Leuven, Department of Chronic Diseases, Metabolism and Ageing, Translational Research for Gastrointestinal Disorders, Leuven, BelgiumUniversity Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, BelgiumKU Leuven, Laboratory of Clinical Immunology, Department of Microbiology and Immunology, Leuven, BelgiumKU Leuven, Department of Chronic Diseases, Metabolism and Ageing, Translational Research for Gastrointestinal Disorders, Leuven, BelgiumUniversity Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, BelgiumKU Leuven, Laboratory of Clinical Immunology, Department of Microbiology and Immunology, Leuven, BelgiumBackground: Mucosal IL-13 Receptor alpha 2 (IL13RA2) mRNA expression is one of the best predictive markers for primary non-responsiveness to infliximab therapy in patients with inflammatory bowel disease (IBD). The objective of this study was to understand how IL-13Rα2, a negative regulator of IL-13 signaling, can contribute to IBD pathology.Methods:IL13RA2 knockout (KO) and wild type (WT) mice were exposed to dextran sodium sulfate (DSS) in drinking water to induce colitis. Furthermore, mucosal biopsies and resection specimen of healthy individuals and IBD patients before the start of anti-tumor necrosis factor (anti-TNF) therapy were obtained for immunohistochemistry and gene expression analysis.Results: After induction of DSS colitis, IL13RA2 KO mice had similar disease severity, but recovered more rapidly than WT animals. Goblet cell numbers and mucosal architecture were also more rapidly restored in IL13RA2 KO mice. In mucosal biopsies of active IBD patients, immunohistochemistry revealed that IL-13Rα2 protein was highly expressed in epithelial cells, while expression was restricted to goblet cells in healthy controls. Mucosal IL13RA2 mRNA negatively correlated with mRNA of several goblet cell-specific and barrier genes, and with goblet cell numbers.Conclusions: The data suggest that IL-13Rα2 on epithelial cells contributes to IBD pathology by negatively influencing goblet cell recovery, goblet cell function and epithelial restoration after injury. Therefore, blocking IL-13Rα2 could be a promising target for restoration of the epithelial barrier in IBD.https://www.frontiersin.org/article/10.3389/fimmu.2018.02983/fullIL13RA2goblet cellsanti-TNF non-responsivenessIBDinflammatory bowel diseaseinfliximab |