Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China.
Chronic Disease Laboratory, Institutes for Life Sciences and School of Medicine, South China University of Technology, Guangzhou, 510006, China.
Clin Rev Allergy Immunol. 2020 Apr;58(2):252-271. doi: 10.1007/s12016-020-08778-6.
Autoimmune liver diseases (AILDs) are potentially life-threatening chronic liver diseases which include autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and recently characterized IgG4-related sclerosing cholangitis. They are caused by immune attack on hepatocytes or bile ducts, with different mechanisms and clinical manifestations. The etiologies of AILDs include a susceptible genetic background, environment insults, infections, and changes of commensal microbiota, but remain complicated. Understanding of the underlying mechanisms of AILDs is mandatory for early diagnosis and intervention, which is of great importance for better prognosis. Thus, animal models are developed to mimic the pathogenesis, find biomarkers for early diagnosis, and for therapeutic attempts of AILDs. However, no animal models can fully recapitulate features of certain AILD, especially the late stages of diseases. Certain limitations include different living condition, cell composition, and time frame of disease development and resolution. Moreover, there is no IgG4 in rodents which exists in human. Nevertheless, the understanding and therapy of AILDs have been greatly advanced by the development and mechanistic investigation of animal models. This review will provide a comprehensive overview of traditional and new animal models that recapitulate different features and etiologies of distinct AILDs.
自身免疫性肝病(AILDs)是潜在危及生命的慢性肝脏疾病,包括自身免疫性肝炎、原发性胆汁性胆管炎、原发性硬化性胆管炎,以及最近被描述的 IgG4 相关硬化性胆管炎。它们是由针对肝细胞或胆管的免疫攻击引起的,具有不同的机制和临床表现。AILDs 的病因包括易感遗传背景、环境损伤、感染和共生微生物群的变化,但仍很复杂。了解 AILD 的潜在机制对于早期诊断和干预至关重要,这对改善预后非常重要。因此,开发了动物模型来模拟发病机制,寻找早期诊断的生物标志物,并尝试治疗 AILD。然而,没有一种动物模型可以完全重现特定 AILD 的特征,尤其是疾病的晚期。某些局限性包括不同的生活条件、细胞组成以及疾病发展和解决的时间框架。此外,啮齿动物中不存在人类中存在的 IgG4。尽管如此,通过开发和对动物模型的机制研究,AILDs 的认识和治疗已经取得了很大的进展。本文将全面综述传统和新型动物模型,这些模型再现了不同 AILD 的不同特征和病因。