The liver is an important immunological organ that controls systemic tolerance. The liver harbors professional and unconventional antigen-presenting cells that are crucial for tolerance induction and maintenance. Orchestrating the immune response in homeostasis depends on a healthy and well-toned immunological liver microenvironment, which is maintained by the crosstalk of liver-resident antigen-presenting cells and intrahepatic and liver-infiltrating leukocytes. In response to pathogens or autoantigens, tolerance is disrupted by unknown mechanisms. Intrahepatic parenchymal and nonparenchymal cells exhibit unique antigen-presenting properties. The presentation of microbial and endogenous lipid-, metabolite- and peptide-derived antigens from the gut via conventional and nonconventional mechanisms can educate intrahepatic immune cells and elicit effector responses or tolerance. Perturbation of this balance results in autoimmune liver diseases, such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Although the exact etiologies of these autoimmune liver diseases are unknown, it is thought that the disruption of tolerance towards self-antigens and microbial metabolites and lipids, as well as alterations in bile acid composition, may result in changes in effector cell activation and polarization and may reduce or impair protective anti-inflammatory regulatory T and B cell responses. Additionally, the canonical and noncanonical transmission of antigens and antigen:MHC complexes via trogocytosis or extracellular vesicles between different (non) immune cells in the liver may play a role in the induction of hepatic inflammation and tolerance. Here, we summarize emerging aspects of antigen presentation, autoantibody production, and the application of novel therapeutic approaches in the characterization and treatment of autoimmune liver diseases.

肝脏是控制全身耐受性的重要免疫器官。肝脏拥有专业和非常规的抗原呈递细胞，这些细胞对于耐受诱导和维持至关重要。在体内平衡中协调免疫反应取决于健康和良好的免疫肝脏微环境，这是由肝脏驻留抗原呈递细胞与肝内和肝脏浸润白细胞的串扰维持的。响应病原体或自身抗原，耐受性被未知机制破坏。肝内实质细胞和非实质细胞表现出独特的抗原呈递特性。微生物和内源性脂质的表现，通过常规和非常规机制从肠道代谢物和肽衍生的抗原可以训练肝内免疫细胞并引发效应反应或耐受。这种平衡的紊乱导致自身免疫性肝病，如自身免疫性肝炎、原发性胆汁性胆管炎和原发性硬化性胆管炎。虽然这些自身免疫性肝病的确切病因尚不清楚，但人们认为对自身抗原和微生物代谢物和脂质的耐受性破坏，以及胆汁酸组成的改变，可能导致效应细胞活化和极化的变化和可能减少或损害保护性抗炎调节 T 和 B 细胞反应。此外，抗原和抗原的规范和非规范传输：MHC 复合物通过肝脏中不同（非）免疫细胞之间的吞噬作用或细胞外囊泡可能在诱导肝脏炎症和耐受中起作用。在这里，我们总结了抗原呈递、自身抗体产生以及新型治疗方法在自身免疫性肝病的表征和治疗中的应用等新兴方面。