Background and aims Hepatic disorders are frequent in patients with systemic lupus erythematosus (SLE), yet the aetiology and pathogenesis of liver injury in SLE remains unclear. The present study primarily aimed to understand the cellular and molecular mechanisms involved in the expression of liver damage in SLE.
Methods We analysed clinical and serological characteristics of 404 SLE patients with liver dysfunction, and determined the pathogenesis of liver damage in SLE by using lupus-prone mice and a novel animal model of liver injury induced by lupus serum IgG.
Results 22.5% of SLE patients have liver dysfunction, and even 38% of them have lupus-hepatitis. There are a large amount of inflammatory cells around the portal areas of the livers, apoptotic hepatocytes and IgG deposition in the liver in lupus-prone mice. Liver injury was successfully established by intrahepatic injection of lupus serum IgG. Immune complexes (ICs) stimulated Kupffer cells (KCs) to secrete TNF-α involved in the development of inflammation and apoptosis in liver. IFN-γ produced by activated natural killer cells (NKs) directly mediated liver damage and also enhanced the TNF-α-mediated apoptotic pathway. The depletion of KCs and NKs abolished apoptosis induced by ICs in liver, suggesting that KCs and NKs have a synergic effect on liver injury.
Conclusions Our findings demonstrated that liver injury was induced by hepatic IgG deposition in SLE and innate immune cells and their products exert an important role in the development of liver injury in SLE. Our results may promote to develop potential therapeutic strategies in prevention and treatment of liver injury in SLE.
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