Table 2. Structural biology and function of a healthy mucosal barrier.
| Barrier compartments | Barrier functions | Functional & cellular elements | References |
|---|---|---|---|
| Mucins | I. Cover, capture, deflect, remove | Loose mucin labyrinth, sterile dense adherent mucin, mucin transient | (1,4-6) |
| II. Neutralize and preserve | Neutralize using IgA, anti-microbial agents; preserve epithelium using trefoil factors (TFF1, TFF2, TFF3) | (13,17-25) | |
| Single cell epithelium | III. Antigen & non-antigen surveillance, detection, barrier lubrication & sustenance | Sample surveillance by αβ-IEL, δγ-IEL, M-cells, dendritic cells, goblet cells; detect mucin disturbance by epithelial transmembrane mucin; lubricate and sustain epithelium by goblet cells producing mucin, trefoil factors; tuft cells and enteroendocrine cells. | (1-6,9,10,18,19,26-36) |
| IV. Cap and close off luminal contents | Epithelial cells with toll-like receptors, tight junctions, epithelial cytokine production, apical transmembrane mucin & cytosol signaling, basolateral growth factors | (1,18,37-44) | |
| Lamina propria and submucosa to subserosa | V. Pre-emptive immune actions | ILC—class I, II, III interacting with epithelial cells, IEL’s, goblet cells, dendritic cells, M-cells | (7,11,30,45-47) |
| VI. Adaptive counter-attack immune actions | Monocytes, macrophages, mast cells, B-lymphocytes, T-lymphocytes, inflammasome formation | (7,17,31,45,48,49) | |
| VII. Host warning and eliminate effluent | Enteric glial neurons with 2 classes of voltage-gated receptors (ASIC, TRPV) on afferent neurons, with input to efferent neurons that are responsive to cytokine secretions from IEL, epithelial cells, mast cells and ILC’s; these neurons extend from the epithelial cell layer (including tuft cells and enteroendocrine cells) downward into the submucosal plexus and myenteric plexus, with functions for sensory, epithelial, vascular, pain, nausea, emesis and motility | (50-65) |
IEL, intra-epithelial lymphocytes; ILC, immune lymphoid cells; ASIC, acid sensing ion channels; TFF, trefoil factors; TRPV, transient receptor potential vanilloid.