title: Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip.
abstract: The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed.
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: J M
authors.initials: JM
authors.lastname: Williams
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: C A
authors.initials: CA
authors.lastname: Duckworth
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: M D
authors.initials: MD
authors.lastname: Burkitt
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, United Kingdom.
authors.forename: A J M
authors.initials: AJ
authors.lastname: Watson
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: B J
authors.initials: BJ
authors.lastname: Campbell
authors.affiliation: Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom Mark.Pritchard@liverpool.ac.uk.
authors.forename: D M
authors.initials: DM
authors.lastname: Pritchard
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000473:pathology*; D007421:Intestine, Small / Q000473:pathology; D051379:Mice; D008871:Microvilli / Q000473:pathology; D016328:NF-kappa B / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha
keywords: bacterial; digestive tract; genetically engineered mice; imaging; immunohistochemistry; immunologic; inflammation; nutritional