Abstract
Intestinal epithelial cells play a fundamental role in maintaining homeostasis. Shedding of intestinal cells in a controlled manner is critical to maintenance of barrier function. Barrier function is maintained during this shedding process by a redistribution of tight junctional proteins to facilitate closure of the gap left by the shedding cell. However, despite the obvious importance of epithelial cell shedding to gut health, a central question is how the extrusion of epithelial cells is achieved, enabling barrier integrity to be maintained in the healthy gut and restored during inflammation remains largely unanswered. Recent studies have provided evidence that excessive epithelial cell shedding and loss of epithelial barrier integrity is triggered by exposure to lipopolysaccharide or tumor necrosis factor alpha. Subsequent studies have provided evidence of the involvement of specific cellular components and signaling mechanisms as well as the functionality of microbiota that can be either detrimental or beneficial for intestinal barrier integrity. This review will focus on the evidence and decipher how the signaling systems through which the mucosal immune system and microbiota can regulate epithelial cell shedding and how these mechanisms interact to preserve the viability of the epithelium.
Highlights
The intestinal barrier separates the body from the contents of the intestine
Epithelial cells undergo apoptosis during the shedding process though it remains unclear whether apoptosis initiates the shedding process or is secondary to detachment from the basement membrane [3] (Figure 1B)
Intraepithelial lymphocytes within the epithelial monolayer have normally been associated with celiac disease; recent date indicate that they may have a central role in epithelial barrier function
Summary
The intestinal barrier separates the body from the contents of the intestine It comprises several elements: a mucus layer containing antibacterial peptides covering the luminal surface of the epithelium; the epithelial cell monolayer, junctional proteins, and intraepithelial lymphocytes (IELs); and a subepithelial layer of extracellular matrix and mesenchymal cells including myofibroblasts and fibroblasts. There is a continuous shedding of epithelial cells from villus tip or colonic surface as a result of migration of the epithelial cell up the crypt–villus axis from stem cells at the base of the crypt (Figure 1A). The shedding of epithelial cells is counter-balanced by cell division in the crypt region of the villi to maintain homeostasis and a strict single layer epithelium and integrity of the crypt–villus axis [2,3,4]. In contrast to physiological cell shedding, tumor necrosis factor alpha (TNFα)-induced apoptotic cell shedding often results in the shedding of multiple adjacent
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