Table 1.
Role of immune cells involved in gut homeostasis and abnormalities produced in cirrhosis.
| Cell type | Immune function | References | Intestinal mucosa abnormalities in cirrhosis | References | |
|---|---|---|---|---|---|
| Intestinal epithelial cells | Enterocytes | Form TJ structures; produce antimicrobial molecules (Reg3γ and Lypd8); express pIgR | (4) | Shedding and apoptosis, decreased TJs and AMPs Reg3β and Reg3γ | (5–7) |
| Paneth cells | Produce AMPs α-defensin 5 (HD5), HD6 and Reg3γ | (4, 8, 9) | Defective production of AMPs (α-defensins and Reg3 proteins) | (6, 7, 10, 11) | |
| Goblet cells | Produce mucin and anti-inflammatory molecules (trefoil factor 3, RELMbeta) | (4, 12) | Loss of goblet cells and decreased MUC2 resulting in reduced mucous layer thickness | (13) | |
| Microfold (M) cells | Uptake of antigens | (4, 14) | N/R | ||
| Tuft cells | Sense luminal helminths | ||||
| sIgA (produced by plasma cells) | Binding and retention of bacteria in the intestinal lumen |
(15) | Reduced synthesis in the jejunum and diminished fecal content | (5, 16, 17) | |
| Neutrophils | Elimination of translocated microbes, facilitation of mucosal healing, recruitment of other immune cells | (18, 19) | N/R | ||
| Macrophages | Bactericidal activity, transfer of acquired antigen to DC for presentation to T cells, production of immunoregulatory cytokines IL-10 and TGF-β | (20) | Activated CD14+Trem1+iNOS+ secreting IL-6, IL-8, NO and MCP-1 | (21) | |
| Dendritic cells | Maintenance of tolerogenic state; initiation and differentiation of adaptive immune responses | (22) | Deficient phagocytosis, migration capacity, and TNF-α production | (23) | |
| Eosinophils | Cytotoxic effect, modulation of B and T cells | (24, 25) | N/R | ||
| Mast cells | Innate response, antigen clearance, release of histamine, proteases, and prostaglandins | (26, 27) | N/R | ||
| ILC1 (including NK cells) | Cytotoxicity, macrophage activation | (28, 29) | Expanded showing increased IFN-γ production | (5) | |
| ILC2 | Immunity to helminths | (28) | N/R | ||
| ILC3 | Host defense against extracellular bacteria and fungi | (28) | Reduced IL-22 production by ILC3s which promotes diminished intestinal Reg3γ expression, resulting in bacterial translocation to the liver | (30) | |
| iNKTs | Response to lipid antigen, production of cytokines and chemokines | (28) | Expanded in intestinal lamina propria, but reduced IL-17 production | (5) | |
| Tgamma-delta | Defense against infection and wound healing | (31) | Expanded in intestinal lamina propria | (5) | |
| MAIT cells | Modulation of host-microbial interplay, antibacterial immunity | (32, 33) | N/R | ||
| Th CD4+ | Th17 | Neutrophilic inflammation, response to extracellular bacteria and fungi | (34–39) | Diminished in the lamina propria | (5) |
| Th1 | Monocytic inflammation, response to intracellular bacteria, protozoans, and viruses | Increased production of IFN-γ in the small intestine | (5) | ||
| Th22 | Mucosal host defense, secretion of beta-defensins | (40) | N/R | ||
| Treg | Tissue homeostasis and tolerogenic cytokine production | (41–44) | Expanded in the lamina propria | (5) | |
| Tc CD8+ | Cytotoxic activity | (45) | Expanded showing high IFN-γ production | (5) | |
| Memory T cells | Central memory T cells | Re-exposure with their cognate antigen recirculating between secondary lymph organs and blood | (46) | Expanded in the small intestine | (5) |
| Effector memory T cells | Re-exposure with their cognate antigen recirculating between peripheral circulation and tissue | Expanded in the small intestine | |||
N/R, none reported.