Ubiquitin E3 ligase A20 contributes to maintaining epithelial barrier function

Abstract

Background and Aims: Epithelial barrier dysfunction is involved in the pathogenesis of allergic diseases; the mechanism is to be further understood. Ubiquitin E3 ligase A20 (A20) plays a role in maintaining the homeostasis in the body. This study aims to investigate the role of A20 in maintaining the epithelial barrier function. Methods: Human intestinal epithelial cell line, Caco-2 cells, was cultured to monolayers to test the endocytosis and degradation of a model allergen, ovalbumin (OVA). The role of A20 in the endosome/lysosome fusion in epithelial cells was tested with A20-sufficient and A20-deficient Caco-2 cells and visualized by immunocytochemistry. Results: Caco-2 cells could endocytose exogenous allergens (OVA) in culture. The endocytic OVA was degraded in A20-sufficient Caco-2 cells via the mechanism of endosome/lysosome fusion, while the A20-deficient Caco-2 monolayers converted the OVA to the basal compartment of transwells, which conserved the antigenicity reflected by that it induced T cell proliferation in an allergen-specific manner. A20 was required in the fusion of endosomes and lysosomes. Conclusion: A20 contributes to maintaining the epithelial barrier function. Copyright © 2012 S. Karger AG, Basel.