Cell types in small intestine and colon

As this thesis focuses on the microbiota in the small intestine and colon, the cell types in the small intestine and colon will be described in the following section.

Figure 2. Overview of epithelial cells and immune cells in the small intestine (left) and colon (right). In the middle, a Peyer’s patch with follicle-associated epithelium. Figure from Peterson and Artis 2014 (3).

Reprinted with permission from Nature Springer. IEC; Intestinal epithelial cell, IESC; intestinal epithelial stem cell niche incl crypt-base-columnar (CBC) stem cells and transit amplifying cells. AMPs; antimicrobial peptides, sIgA; secretory Immunoglobulin A, TFF3; trefoil factor 3, DC; dendritic cell.

5.1.2.1. CBC stem cell

Crypt-base-columnar (CBC) stem cells are pluripotent intestinal epithelial stem cells, which can self-renew and differentiate into any specialised intestinal epithelial cell (4).

The marker for CBC cells is Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), and sometimes these cells are referred to as LGR5+ stem cells (5). CBC stem cells

are located in the base of the crypts and divide every 24 hours into transit amplifying cells which further divides and differentiate or provide new CBC stem cells (5).

5.1.2.2. Transit amplifying cell

Transit amplifying cells are daughter cells of the CBC stem cells and are localised further up in the crypts towards the villi (3). Transit amplifying cells divide every 12 hours (4).

The cells then differentiate into specialised cells such as enterocytes and migrate up along the villi as the surface cell-layer of the intestine shred off (3). The life span of a cell from birth, differentiation, migration and until it is shred of is five days (4).

5.1.2.3. Enterocyte

Absorptive enterocytes are the most abundant cell-type in the intestine (Figure 2).

Enterocytes are columnar cells, in the small intestine, they have a characteristic brush border consisting of microvilli protruding into the lumen (1). Enterocytes are specialised cells absorbing and digesting luminal contents, but can also secrete some AMPs such as C-type lectin regenerating islet derived protein (REG) 3g which stimulate segregation between gut microbiota and epithelium (3, 6).

5.1.2.4. Enteroendocrine cell

Enteroendocrine cells are secretory intestinal epithelial cells producing hormones that regulate digestive functions, and they act as a mediator between the central and enteric neuroendocrine system (Figure 2) (3). Numerous subtypes exist, producing hormones such as gastrin, somatostatin, ghrelin, serotonin, cholecystokinin (CCK), glucose-dependent insulinotropic peptide, glucagon-like peptides and peptide YY (7).

5.1.2.5. Goblet cell

Goblet cells are secretory intestinal epithelial cells which produce and secrete glycoproteins, including mucin2 (MUC2) into the intestinal lumen forming mucus layers which act as the first line defence against luminal contents including microbiota (3, 6).

Goblet cells also produce trefoil factor 3 (TFF3), which contributes to mucin organization by mucin crosslinking and epithelial repair stimulation (Figure 2). Additionally, goblet cells allow passage of antigens from the lumen to specialised dendritic immune cells (8).

The number of goblet cells increases throughout the GI-tract and is much more prevalent in the colon than in the small intestine (1).

5.1.2.6. Paneth cells

Paneth cells are localised in the crypt base and are long-lived differentiated intestinal epithelial cells which produce and secrete antimicrobial peptides (AMPs) (8). The Paneth cell is the only cell type that differentiates and migrates down towards the crypt base, where the oldest Paneth cells are localized (5). Paneth cells are renewed every 3-6 weeks (5). Paneth cells are primarily localised in the small intestine and not in the colon, however during inflammatory processes, metaplastic Paneth cells occur in the colon.

The AMPs are located in the granules of Paneth cells. Secretion of AMPs might occur continuously, with increased secretion after various stimulation, such as bacteria, bacterial products or cholinergic agonists (9). AMPs produced in Paneth cells include a-defensins, lysozyme, secretory group IIA phospholipase A2 (sPLA2), REG3a (9). AMPs act bactericidal and many kill targeted microorganisms, some also act towards fungi, viruses and protozoa (9).

5.1.2.7. Peyer’s patch

Peyer’s patches consist of aggregated lymphoid follicles encircled by follicle-associated epithelium (FAE) that contains M cells (Figure 2) (10). Peyer’s patches are dominantly located in the distal ileum and increase in size and density from the jejunum to ileum (1). The number of Peyer’s patches declines after youth. The Peyer’s patches communicate with mesenteric lymph nodes (MLN) through lymphocytes that enter the Peyer’s patch as naïve lymphocytes and leave as either naïve or active lymphocytes (10).

The FAE also harbour an extensive abundance of immune cells; infiltrated B-cells, T-cells, macrophages and dendritic cells.

5.1.2.8. M cell

Microfold cells, or M cells, are specialized intestinal epithelial cells are primarily located in FAE in close proximity to the Peyer’s patches (Figure 2). M cells transport live bacteria, fungi, viruses, parasites as well as non-infectious particles and antigens from the lumen through the apical membrane to the basolateral surface for presentation to the underlying immune system, both through non-specific transcytosis and by specific receptor-mediated microbial uptake (3, 11). Additionally, M cells transport secretory IgA (sIgA) produced in plasma cells from the basolateral membrane to the intestinal lumen.

Interestingly, M cells also have IgA receptors enabling them to capture IgA coated bacteria and present them to the immune system (10). On the contrary, M cells can also be a gateway exploited by intestinal pathogens. In fact, many typical enteric pathogen bacteria have been found to adhere to M cells during invasion, among these are Escherichia coli and Yersinia (10).

5.1.2.9. Tuft cell

Tuft cells, or brush cells, are chemosensory cells. They were initially identified by electron microscopy due to their characteristic morphology consisting of a tubulovesicular system connected to a tuft of long microvilli protruding into the lumen (8). The number of tuft cells increases significantly during parasite infections, where tuft cells produce IL-25 initiating a type 2 immune response (8).