The intestines are a long, continuous tube consisting of the small intestine, large intestine and the rectum. Their role is to absorb nutrients as well as aid the digestion of food (Hoffman, 2018). Epithelial cells are specialised components for a variety of organs. They offer a diverse range of functions due to distinct adaptions but can still be classified by some common structural features. Their main functions are absorption, secretion or to act as a barrier (Lowe and Anderson, 2015). Intestinal epithelial cells are located within the mucosa layer of the intestines, existing as a single layer of cells lining the intestinal epithelium (Kong, Zhang and Zhang, 2018).
Enterocytes are the most abundant of the intestinal epithelial cells – comprising of a simple, columnar shape, they are specialised to aid nutrient absorption and digestion in the intestines (Kong, Zhang and Zhang, 2018). For example, enzymes expressed on their surface ‘perform terminal digestion in concurrence with luminal hydrolysis of food polymers by pancreatic enzymes’ (Hooper, 2015). Through non-selective fluid phase pinocytosis and selective receptor-mediated endocytosis, enterocytes ‘transport macromolecules, from the intestinal epithelium to the underlying tissue via the transcellular pathway’ (Johnson et al., 2012).
Goblet cells ‘comprise around 10% of all intestinal epithelial cells’ and are the major secretory cell lineage within the intestines (Kong, Zhang and Zhang, 2018). Named after their ‘wineglass shape’, their organelles are suppressed to the lateral margins to ensure room for the interior mucus-secreting granules, leaving it with a ‘distinctly polarised morphology’ (Wyllie, Hyams and Kay, 2011). These granules are responsible for secreting the major components of mucus, such as mucin. This mucus layer is essential in the lubrication of faeces through the intestines as well as protecting the epithelium from chemical stress (Hooper, 2015). The function of goblet cells in the intestinal epithelium is similar to its function in the bronchi, whereby it produces mucus to trap microbes within the inhaled air (Alberts, Johnson and Lewis, 2002). However, the mucus residue is eventually brushed away by cilia cells, indicating that the goblet cells in the intestines are more specialised in order to provide constant protection to the intestinal epithelium.
Enteroendocrine cells are sparsely distributed in the small intestine and ‘comprise about 1% of the intestinal epithelial cell population’ (Hooper, 2015). They are tall, columnar cells, with ‘prominent cytoplasmic secretory granules in the basal region’ responsible for secretion of amine and peptide hormones. These peptides are synthesised as precursors in the rough endoplasmic reticulum before being transported to the Golgi apparatus to be packed in the secretory granules (Johnson et al., 2012). Their secretion is controlled by ‘microvilli sensory apparatus that detects a change in the chemical content of the lumen’ where they then discharge the hormones into the basolateral side of the cell. These hormones can then diffuse the short distance to the capillary bed where it can then exert paracrine effects locally in the gastrointestinal tract. (Johnson et al., 2012). The entirety of the apical membrane is covered with these microvilli, which also increases the surface area of the epithelium, furthermore, increasing the overall rate of absorption within the intestines.
The intestinal epithelial cells also play an essential role in the gut immune system. Enterocytes express cytokine receptors allowing them to sample foreign antigens and bacteria within the lumen, directing the immune system to possible harmful pathogens – maintaining the mucosal immune system responsiveness (Remacle and Reusens, 2004). Paneth cells occupy the base of the crypts and release secretory granules responsible for a ‘large proportion of antimicrobial output in the small intestine’ as well as aiding the maintenance of the intestinal epithelium. For example, they secrete -defensins which ‘protect the host from enteric pathogens and reduce bacterial translocation’ (Said, 2018). Also, the mucus layer, produced by the goblet cells, acts as a protective layer from antigens, meaning the goblet cells ‘participate in the uptake and presentation of antigens to immune cells’ (Hooper, 2015).
As a physical barrier between the contents of the lumen and the remainder of the body, the single layer of epithelial cells continuously endures harsh conditions, ultimately leading to their death via apoptosis. Therefore, in order to regulate this barrier, these cells are consistently replaced every 4-5 days by the division of epithelial stem cells in the intestinal crypts. During this division, the cells can then differentiate into the specific epithelial cells (Cooper and Hausman, 2009). The secretion of EGF from Paneth epithelial cells helps regulate epithelial renewal by sustaining proliferating stem cells (Johnson et al., 2012). Thus, ensuring the continuous function of the intestinal epithelium.
The intestinal epithelium maintains its shape by the interaction and attachment of neighbouring cells in cell-cell adhesion. Cell-cell adhesion is ensured by the presence of tight junctions (Remacle and Reusens, 2004). The movement of nutrients into the epithelial cells creates two different extracellular environments on either side of the epithelium lining, these environments are then maintained by the selective permeability of the intestinal epithelium through extracellular pores within the tight junctions (Pollard et al., 2017). Tight junctions are the fusion points between the outer-membrane leaflets of two epithelial cells. They form a tight barrier that maintains the semipermeable properties of these cells and thus completely defining the boundary between the apical and basolateral domains (Holcomb and Ashcraft, 2014). Adherens junctions are a ‘prerequisite for the assembly of tight junctions’ (Pollard et al., 2017). They are ‘the first connections established in developing epithelial sheets’ and use the ‘homophilic interaction of E-cadherins to link adjacent epithelial cells’. The association of Rho family GTPases and protein kinases within these junctions means that the shape of the cells often depends on the presence of them, as well as to regulate the assembly and contraction of the actin cytoskeleton (Pollard et al., 2017). Gap junctions are formed from connexions between plasma membranes of cells, allowing the passage of small signalling molecules, such as calcium (Al-Ghadban et al., 2016). They have been proven to play an important role in many pathophysiological processes as well as ‘buffer concentrations of metabolites amongst cells and transmit regulatory molecules’ (Bennett et al., 1991). Desmosomes link adjacent cells together through their cytoskeletons, holding cells just thirty nanometres apart (Bennett et al., 1991). Through the mediation of cell-cell adhesion and cytoskeleton linkages, desmosomes mechanically integrate cells within tissues and thereby function to resist mechanical stress (Kowalczyk and Green, 2013).