Table 1.
Roles of IDO in animal models for liver injuries.
| Year | Model | IDO status | Study design | Roles of IDO | Effect of IDO immune modulation | References |
|---|---|---|---|---|---|---|
| 2009 | HBV | + | Hepatitis B virus (HBV) transgenic (Tg) mice | Cytotoxic T lymphocytes transduction results in the upregulation of IDO, which might downregulate T-cell responsiveness | HBV infection facilitates the induction of IDO | (15) |
| 2010 | Liver transplantation | + | Rat orthotopic liver transplantations (OLT) | IDO may act as a local immunosuppressive molecule to protect transplanted cells, tissues and organs from immune attack | Protective effect against rat liver transplant rejection | (71) |
| 2010 | Attenuate liver injury | + | α-GalCer-inducedhepatitis | Decrease the number of TNF-α-producing immune cells in the liver | Protective effect against liver injury | (51) |
| 2012 | HBV | + | Hepatitis B virus (HBV)-transgenic (Tg)/IDO-knockout (KO) mice | IDO deficiency attenuated liver injury in HBV-Tg mice injected with HBV-specific CTL | Aggravated HBV | (72) |
| 2012 | Liver transplantation | + | Rat liver transplantation | The IDO level of KCs was closely associated with immune tolerance induction | Protective effect against rat liver transplant rejection | (18) |
| 2012 | Acute hepatic injury | + | CCl4-induced hepatitis model | IDO deficiency exacerbated liver injury in CCl4-induced hepatitis by inducing TNF-α and IL-6 | Protective effect against liver injury | (55) |
| 2013 | Liver injury | NA | High-fat diet-induced hepatic inflammation and fibrosis | The deficiency of IDO may increase T cell activation, either directly or indirectly, by suppressing Tregs and thus contributed to a worsening of hepatic inflammation | Protective effect against hepatic fibrosis | (61) |
| 2014 | Liver injury | NA | The CCl4 liver-injured rats | The level of Trp increased | Biomarker | (73) |
| 2016 | Hepatic fibrosis | + | The CCl4-induced liver fibrosis in Mice | The deficiency of IDO aggravated the CCl4-Inducedliver fibrosis in Mice by suppressing the inflammatory response induced by TNF-α | Protective effect against liver injury | (54) |
| 2016 | Hepatocarcinogenesis | + | DEN-induced hepatocarcinogenesis | IDO up-regulation may contribute to the development and progression of liver carcinogenesisbyinduction of both inflammation and an immunosuppressive microenvironment | Aggravated hepatocarcinogenesis | (70) |
| 2017 | Hepatic fibrosis | UK | CCl4-induced liver fibrosis rat model | Trp level is changed at all time points and could be regarded as effective biomarkers for the early detection of liver fibrosis | Biomarkers | (74) |
| 2017 | Liver fibrosis | Humans,-; mice,+ | CCl4-induced liver fibrosis mice | IDO1 deficiency attenuated CCl4-induced fibrosisthrough Th17 cells down-regulation andTDO compensation | Aggravated liver injury | (56) |
| 2017 | Liver fibrosis | NA | CCl4-induced liver fibrosis rat model | Trplevel was increased | Biomarker | (74) |
| 2018 | Liver injury | NA | ANIT-induced liver injury in rats | Trp was identified as potential biomarkers of cholestasis | Biomarkers | (75) |
| 2020 | Liver injury | UK | CCl4-induced acute liver injury | IDO2 deficiency attenuated CCl4-induced acute liver injury by AHR pathway | Aggravated liver injury | (76) |
| 2020 | Acute immune hepatitis (AIH) | + | ConA-induced AIH mice | 1-MT alleviated murine liver damage with the reduction of inducible nitric oxide synthase and 3-nitrotyrosine expression alleviated murine liver damage | Aggravated liver injury | (65) |
| 2021 | Idiosyncratic drug-induced liver injury (IDILI) | UK | PD-1−/−mouse model of IDILI | 1-D-MT decreased amodiaquine-induced liver injury in femalePD-1−/−mice. | The immuneresponse has many redundant feedback mechanisms that canlead to paradoxical effects | (77) |
| 2021 | BDL | + | BDL mice model | IDO1 affects the process of immune cells recruitment via inhibiting DCs maturation and subsequent T cells proliferation, resulting in the promotion of hepatic fibrosis | Aggravated liver injury | (68) |
In contrast to control group, the increase of IDO expression in model group is expressed as “+,” the decrease of that as “-.” UK, unknown; IDO, indoleamine 2,3 dioxygenase; Kyn, kynurenine; Trp, tryptophan.