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.
Highlights
The intestinal epithelium is a critical component of the gut barrier
A common feature conserved among mammals that possess small intestinal villi[40] is that newly generated intestinal epithelial cells (IECs) within the crypt migrate toward the villus tip region, where loss of senescent epithelial cells occurs in the extrusion zone (Fig. 1)
In vivo confocal imaging in mice has shown that central leucine-rich repeat-containing G protein–coupled receptor 5 (Lgr5)-positive crypt base columnar (CBC) cells maintain a position within the crypt base, while CBC cells in the upper part of the stem cell niche may be passively displaced into the transit-amplifying cell population.[65]
Summary
The small intestinal epithelium allows water, electrolytes, and nutrients to be absorbed from the digesta while functioning as an essential component of the gut barrier. Enterocytes have the highest turnover rate of any fixed-cell population in the body.[28] Mathematical modeling suggests that in the mouse, an estimated 1400 mature enterocytes are shed from a single villus tip in each 24-hour period,[63] equating to 2 Â 108 cells being shed from the small intestine per day. In humans, this daily loss has been estimated at 1011 cells.[63]. They are variably abundant among species, and while exceptionally abundant in some, such as the giant anteater,[79] and prominent in primates, rodents, and the horse,[28] they are absent in dogs, cats, and pigs,[8] which raises questions about the role of these cells in this regard
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