title: Microbial products induce claudin-2 to compromise gut epithelial barrier function.
abstract: The epithelial barrier dysfunction is an important pathogenic feature in a number of diseases. The underlying mechanism is to be further investigated. The present study aims to investigate the role of tight junction protein claudin-2 (Cldn2) in the compromising epithelial barrier function. In this study, the expression of Cldn2 in the epithelial layer of mice and patients with food allergy was observed by immunohistochemistry. The induction of Cldn2 was carried out with a cell culture model. The Cldn2-facilitated antigen internalization was observed by confocal microscopy. The epithelial barrier function in the gut epithelial monolayer was assessed by recording the transepithelial resistance and assessing the permeability to a macromolecular tracer. The results showed that the positive immune staining of Cldn2 was observed in the epithelial layer of the small intestine that was weakly stained in naïve control mice, and strongly stained in sensitized mice as well as patients with food allergy. Exposure to cholera toxin or Staphylococcal enterotoxin B induced the expression of Cldn2 in HT-29 or T84 cells. Cldn2 could bind protein antigen to form complexes to facilitate the antigen transport across the epithelial barrier. Blocking Cldn2 prevented the allergen-related hypersensitivity the intestine. We conclude that the tight junction protein Cldn2 is involved in the epithelial barrier dysfunction.
authors.affiliation: State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.forename: Gui
authors.initials: G
authors.lastname: Yang
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Geng
authors.forename: Yanjuan
authors.initials: Y
authors.lastname: Cao
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Yang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002772:Cholera Toxin / Q000378:metabolism*; D062446:Claudin-2 / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D004768:Enterotoxins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005512:Food Hypersensitivity; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D010539:Permeability; D011485:Protein Binding; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D062446:Claudin-2; D004768:Enterotoxins; C031818:enterotoxin B, staphylococcal; D002772:Cholera Toxin; D000242:Cyclic AMP