Table 1.
Major cell types found in the intestinal epithelium, their major function(s), and impacts seen in the cells during ALD
| Cell type | Layer | Major function(s) | Ald impacts | References |
|---|---|---|---|---|
| Enterocytes | Intestinal epithelium | Cytokine secretion (APRIL, BAFF, TSLP) and response; | Reduced expression of tight junction proteins; | 4-16, 18-27, 30, 31 |
| AMP secretion (REG3γ, REG3ß, cathelicins); | Increased permeability; | |||
| IgA transport (pIgR); | Reduction in expression of REG3γ and REG3ß; | |||
| Formation of tight junctions (occluding, claudins, Junction Adhesion Molecules); | IgA levels reduced; | |||
| Express Lypd8 protein to prevent invasion of flagellated microbiota; | Apoptosis of enterocytes; | |||
| Express fucosylated carbohydrate structures. | α1-2-fucosylation downregulated. | |||
| Goblet cells | Intestinal epithelium | Mucin secretion to form mucus layer; | Mucin production increases in the small intestine; | 46, 51-63 |
| Disperse AMPs (lysozyme C, α-defensins, phospholipases, cryptdins, lectins), IgA, and mucin for mucus protective layer; | Thickening of mucus layer. | |||
| Secrete AMPs (RELM-ß, TFF); | ||||
| Create goblet cell associated-passages (GAPs). | ||||
| M cells | Intestinal epithelium | Transporters of antigens to macrophages and dendritic cells through endocytosis and transcytosis; | Structural changes in M cells; | 64-66, 70 |
| Partner with B lymphocyte. | Further research needed. | |||
| Enteroendocrine cells | Intestinal epithelium | Help with gastrointestinal process through release of peptide hormones; | Increase in the numbers of glucagon and gastric inhibitory peptide (GIP) cells; | 72-77 |
| Release cytokines; | Decreased somatostatin. | |||
| Recognize SCFAs through GPR41, GPR43. | ||||
| Tuft cells | Intestinal epithelium | Produce cytokines (IL-25) to allow communication with intestinal immune cells | Increase in number | 78, 79 |
| Intestinal stem cells | Intestinal epithelium | Replenish themselves along all cell types in the intestinal epithelium; | Dysfunction of signaling; | 32 |
| Maintains barrier. | Reduces replacement of cells. | |||
| Paneth cells | Intestinal epithelium | Produce and release AMPs (lysozyme C, α-defensins, phospholipases, cryptdins, and lectins) | Increase in number in the proximal small intestine; | 10, 11, 35, 40-44, 46-50 |
| AMP α-defensins reduced; | ||||
| REG3 expression reduced. |
Impacts seen during ALD include evidence from human patients and/or evidence from mouse models fed various ethanol diets. Abbreviations: ALD: alcohol-associated liver disease; AMP: anti-microbial peptide; APRIL: A proliferation-inducing ligand; BAFF: B cell-activating factor of the tumor necrosis factor family; GAPs: goblet cell associated-antigen passages; GIP: gastric inhibitory peptide; GPR: G protein receptors; IgA: immunoglobulin A; Lypd8: Ly6/Plaur domain-containing 8; M cell: microfold cell; pIgR: polymeric immunoglobulin receptor; REG3: regenerating islet-derived 3; RELM- ß resistin-like molecule ß; SCFAs: Short-chain fatty acids; TFF: trefoil factor; TSLP: thymic stromal lymphopoietin.