AUTHOR=Verstockt Bram , Perrier Clémentine , De Hertogh Gert , Cremer Jonathan , Creyns Brecht , Van Assche Gert , Ferrante Marc , Ceuppens Jan L. , Vermeire Séverine , Breynaert Christine 

TITLE=Effects of Epithelial IL-13Rα2 Expression in Inflammatory Bowel Disease

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02983

DOI=10.3389/fimmu.2018.02983

ISSN=1664-3224

ABSTRACT=<p><bold>Background:</bold> Mucosal IL-13 Receptor alpha 2 (<italic>IL13RA2</italic>) 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.</p><p><bold>Methods:</bold><italic>IL13RA2</italic> 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.</p><p><bold>Results:</bold> After induction of DSS colitis, <italic>IL13RA2</italic> 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 <italic>IL13RA2</italic> 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 <italic>IL13RA2</italic> mRNA negatively correlated with mRNA of several goblet cell-specific and barrier genes, and with goblet cell numbers.</p><p><bold>Conclusions:</bold> 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.</p>