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Front. Immunol. | doi: 10.3389/fimmu.2018.02983

Effects of epithelial IL-13Rα2 in inflammatory bowel disease

 Bram Verstockt1, 2, Clementine Perrier2, 3, Gert De Hertogh4, Jonathan Cremer3, Brecht Creyns3, Gert Van Assche1, 2, Marc Ferrante1, 2, Jan Ceuppens3, Séverine Vermeire1, 2 and  Christine Breynaert3*
  • 1Department of Gastroenterology & Hepatology, University Hospitals Leuven, Belgium
  • 2Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Belgium
  • 3Department of Microbiology and Immunology, KU Leuven, Belgium
  • 4University Hospitals Leuven, Belgium

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 of healthy individuals and IBD patients before the start of 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 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 agent for restoration of the epithelial barrier in IBD.

Keywords: IL13RA2, Goblet cell, anti-TNF non-responsiveness, IBD, IBD – Inflammatory bowel diseases

Received: 24 Oct 2018; Accepted: 04 Dec 2018.

Edited by:

Eric Cox, Ghent University, Belgium

Reviewed by:

Hiroshi Nakase, School of Medicine, Sapporo Medical University, Japan
Britta Siegmund, Charité Medical University of Berlin, Germany  

Copyright: © 2018 Verstockt, Perrier, De Hertogh, Cremer, Creyns, Van Assche, Ferrante, Ceuppens, Vermeire and Breynaert. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Christine Breynaert, Department of Microbiology and Immunology, KU Leuven, Leuven, BE-3000, Belgium, christine.breynaert@uzleuven.be