Table 1.
Effects of dysregulated immune crosstalk pathways in MASLD mouse models
| Pathway | Model used | Diet Fed | Effects on MASLD (compared to WT) | Ref |
|---|---|---|---|---|
| CD28/B7.1, B7.2 | CD28−/− mice (C57BL/6) | HFD (60% kcal fat) |
↓hepatic steatosis; ↓hepatic inflammation; ↓hepatocellular damage |
181 |
| B7.1−/−B7.2−/− mice (C57BL/6) | HFD (60% kcal fat) |
↑hepatic steatosis; ↑hepatic inflammation; ↓hepatocellular damage |
182 | |
| Antibody-mediated depletion of B7.1 and B7.2 in wildtype mice (C57BL/6) | HFD (60% kcal fat) | ↓hepatic steatosis; ↓hepatic inflammation | 182 | |
| 4–1BB/4–1BBL | 4–1BB−/− mice (C57BL/6) | HFD (60% kcal fat) | ↓hepatic steatosis; ↓hepatic inflammation | 190 |
| OX40/OX40L | OX-40−/− mice (C57BL/6) | HFD (45% kcal fat) | ↓hepatic steatosis; ↓hepatic inflammation | 195 |
| Rag2−/−IL2rg−/− mice (C57BL/6) adoptively transferred with OX40-deficient T cells | HFD (45% kcal fat) | ↓hepatic steatosis; ↓hepatic inflammation | 195 | |
| CD40/CD40L | CD40−/− mice (C57BL/6) | HFD (55% kcal fat) | ↑hepatic steatosis; ↓hepatic inflammation | 201, 202 |
| wildtype mice (C57BL/6) adoptively transferred with Rag1−/− and CD40−/− BM cells | HFD (45% kcal fat) | ↑hepatic steatosis | 202 | |
| CD40fl/fl CD11c-Cre mice (C57BL/6) | HFD (54% kcal fat) |
↑hepatic steatosis; ↑hepatocellular damage; ↓hepatic Treg accrual |
200 | |
| CD40fl/fl CD11c-Cre mice (C57BL/6) | NASH diet (40% kcal fat, 20% kcal fructose, 2% kcal cholesterol) | ↓hepatic inflammation; ↑hepatocellular damage | 200 | |
| CD40L−/− mice (C57BL/6) | HFD (23% kcal fat) | ↑↓hepatic steatosis | 204, 205 | |
| CD40L−/− mice (BALB/c) | Olive oil administration (6.6 mL/kg of body weight, 3 times/week via oral gavage) | ↑hepatic steatosis | 203 | |
| Fas/FasL | Fasfl/fl Albumin-Cre mice (C57BL/6) | HFD (58% kcal fat) | ↓hepatic steatosis | 215 |
| IFN-I/IFNAR | IFNAR1−/− mice (C57BL/6) | HFD (60% kcal fat) | ↓hepatic steatosis | 228 |
| IFNARfl/fl Albumin-Cre mice (C57BL/6) | MCD diet | ↑hepatic steatosis; ↑hepatic inflammation | 229 | |
| IRF3−/− mice (C57BL/6) | HFD (61.6% kcal fat) | ↑hepatic steatosis; ↑hepatocellular damage | 231 | |
| IRF5flfl Lyz2-Cre mice (C57BL/6) | MCD diet |
↓hepatocellular damage; ↓hepatic inflammation; ↓cirrhosis |
232 | |
| IRF5flfl Lyz2-Cre mice (C57BL/6) | CCl4 (0.5 μL/g diluted 1:5 in olive oil; 2 times/week) |
↓hepatocellular damage; ↓hepatic inflammation; ↓cirrhosis |
232 | |
| IRF9−/− mice (C57BL/6) | HFD (61.6% kcal fat) | ↑hepatic steatosis | 230 | |
| APRIL, BAFF/BAFF-R, BCMA, TACI | APRIL−/− mice (C57BL/6) | HFD (60% kcal fat) | ↓hepatocellular damage | 251 |
| BAFF-transgenic mice (C57BL/6) | HFD (60% kcal fat) | ↓hepatocellular damage | 251 | |
| BAFF−/− mice (C57BL/6) | HFD (60% kcal fat) |
↓hepatic steatosis; ↓hepatic inflammation; ↓cirrhosis |
254 | |
| Antibody-mediated neutralization of BAFF in wildtype mice (C57BL/6) | MCD diet |
↓hepatic steatosis; ↓hepatic inflammation; ↓hepatocellular damage |
157 | |
| TACI-Ig mice (C57BL/6) | MCD diet | ↓hepatic inflammation | 157 | |
| TACI-Ig mice (C57BL/6) | CDAA diet | ↓cirrhosis | 157 | |
| IL-6/IL-6 receptor | Antibody-mediated neutralization of IL-6 receptor in wildtype mice (C57BL/6) | MCD diet | ↑hepatic steatosis; ↓hepatocellular damage | 266 |
HFD, high fat diet; MCD, methionine choline deficient; CDAA, choline deficient and amino acid defined; IFNAR, IFN-I receptor; IRF, interferon regulatory factor; BM, bone marrow. Red upwards arrows indicate augmentation of phenotype. Blue downwards arrows indicate attenuation of phenotype.