ABSTRACT
Deficits in gastrointestinal (GI) paracellular permeability has been implicated in etiology of Inflammatory Bowel Disease (IBD), and E-cadherin, a key component of the epithelial junctional complex, has been implicated in both barrier function and IBD. We have previously described antibodies against E-cadherin that activate cell adhesion, and in this study, we show that they increase transepithelial electrical resistance in epithelial cell monolayers in vitro. We therefore tested the hypothesis that adhesion activating E-cadherin mAbs will enhance epithelial barrier function in vivo and limit progression of inflammation in IBD. Activating mAbs to mouse E-cadherin were tested in different mouse models of IBD including the IL10-/- and adoptive T cell transfer models of colitis. Previously established histological and biomarker measures of inflammation were evaluated to monitor disease progression. Mouse E-cadherin activating mAb treatment reduced total colitis score, individual histological measures of inflammation, and other hallmarks of inflammation compared to control treatment. Activating mAbs also reduced the fecal accumulation lipocalin2 and albumin content, consistent with enhanced barrier function. Therefore, E-cadherin activation could be a potential strategy for limiting inflammation in UC.
Acknowledgments
Animal care and procedural support: SCRI core facility. Crohn’s and Colitis Foundation for visiting research fellowship award to CB. This study was supported by grant R35GM122467 from the National Institutes of Health to BMG.
Author Contributions
Conceived the idea: CB and BMG. Experimental method design: CB and BMG. Performed the experiments: CB. Antibody generation: LSC. Analyzed the data: CB and BMG. Manuscript figure preparation, writing, editing, and manuscript revision: CB and BMG. Supervision of antibody generation: BMG
Competing Interests:
The authors have declared that no competing interests exist.
Supplementary material
Supplemental data for this article can be accessed on the publisher’s website