title: Enteroendocrine cells are specifically marked by cell surface expression of claudin-4 in mouse small intestine.
abstract: Enteroendocrine cells are solitary epithelial cells scattered throughout the gastrointestinal tract and produce various types of hormones, constituting one of the largest endocrine systems in the body. The study of these rare epithelial cells has been hampered by the difficulty in isolating them because of the lack of specific cell surface markers. Here, we report that enteroendocrine cells selectively express a tight junction membrane protein, claudin-4 (Cld4), and are efficiently isolated with the use of an antibody specific for the Cld4 extracellular domain and flow cytometry. Sorted Cld4+ epithelial cells in the small intestine exclusively expressed a chromogranin A gene (Chga) and other enteroendocrine cell-related genes (Ffar1, Ffar4, Gpr119), and the population was divided into two subpopulations based on the activity of binding to Ulex europaeus agglutinin-1 (UEA-1). A Cld4+UEA-1- cell population almost exclusively expressed glucose-dependent insulinotropic polypeptide gene (Gip), thus representing K cells, whereas a Cld4+UEA-1+ cell population expressed other gut hormone genes, including glucagon-like peptide 1 (Gcg), pancreatic polypeptide-like peptide with N-terminal tyrosine amide (Pyy), cholecystokinin (Cck), secretin (Sct), and tryptophan hydroxylase 1 (Tph1). In addition, we found that orally administered luminal antigens were taken up by the solitary Cld4+ cells in the small intestinal villi, raising the possibility that enteroendocrine cells might also play a role in initiation of mucosal immunity. Our results provide a useful tool for the cellular and functional characterization of enteroendocrine cells.
authors.affiliation: Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nagatake
authors.affiliation: Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Fujita
authors.affiliation: Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Minato
authors.affiliation: Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hamazaki
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D053379:Chromogranin A / Q000378:metabolism; D062506:Claudin-4 / Q000235:genetics / Q000378:metabolism*; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D007421:Intestine, Small / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009928:Organ Specificity
chemical_list: D053379:Chromogranin A; D062506:Claudin-4; C568158:Cldn4 protein, mouse