Table 1.
Mediators of immune cells adhesion and clinical relevance in NASH
| LSEC Adhesion Molecules |
Leukocyte Binding Partner |
Mice Studies |
Human Studies: | ||
|---|---|---|---|---|---|
| Inhibition | Mouse Model | Liver Histology | Adhesion Molecule Serum Level/Hepatic Expression | ||
| VCAM-1/MAdCAM-1 | ITGα4β1 ITGα4β7 ITGα9β1 |
Anti-ITGα4β1 Ab | HFD | Decreased myeloid cell hepatic infiltration (11) | VCAM-1 serum level was an independent predictor for ≥ F2 fibrosis in NAFLD (34). VCAM-1 hepatic expression was increased in NASH (12). MAdCAM-1 hepatic expression was elevated in NASH and correlated with ITGα4β7(35) |
| Anti-ITGα4β7 Ab | WD | Decreased CD4+ T-cell hepatic infiltration and fibrosis (35) |
|||
| Anti-ITGβ1 Ab | FFC | Decreased MoMF-associated liver inflammation and fibrosis (10) | |||
| Anti-VCAM1 Ab AGI-1067 |
FFC | Reduced MoMF-associated liver inflammation and fibrosis (12) | |||
| ICAM1/ MadCAM1 | L-Selectin (CD62L) | CD62L−/− Anti-CD62L Ab |
HFD or MCD | Decreased steatosis, increased Treg (36) | Soluble CD62L serum level was increased in NASH CD62L hepatic expression correlated with NASH activity (36) |
| VAP-1 | Unknown | VAP-1−/− Anti VAP-1 Ab |
WD, or MCD | Decreased hepaticinflammatory cell infiltrate and fibrosis(33) | VAP-1 serum level correlated with histological severity in NAFLD (33) |
FFC, fat, fructose- and cholesterol-rich diet; HFD, high-fat diet; ICAM1, intercellular adhesion molecule 1; ITG, integrin; LSEC, liver sinusoidal endothelial cell; MAdCAM-1, mucosal address in cell adhesion molecule-1; MoMF; monocyte-derived macrophage; Treg cell, regulatory T cell; VAP1, vascular adhesion protein; VCAM-1, vascular cell adhesion molecule 1; WD, Western diet.