Snyder Institute, Immunology Research Group, Division of Gastroenterology, Liver Unit, University of Calgary, Calgary, Alberta, Canada T2N 4N1
Autoimmun Rev. 2011 Oct;10(12):793-800. doi: 10.1016/j.autrev.2011.06.003. Epub 2011 Jun 28.
The three main broad categories of autoimmune liver disease are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). The etiologies of these diseases are still incompletely understood, but seem to involve a combination of immune, genetic and environmental factors. Although each of these diseases has relatively distinct clinical, serologic and histological profiles, all of them share common pathways of immune-mediated liver injury. The development of autoimmune liver diseases is thought to be due to an imbalance of proinflammatory and anti-inflammatory immune responses within the liver, with proinflammatory immune responses being upregulated and anti-inflammatory ones downregulated. The available evidence, suggest that during autoimmune responses within the liver, "self" antigens are presented by antigen presenting cells (APCs) which then activate, directly and/or indirectly, NKT cells and other innate immune cells within the liver. Importantly, the hepatic innate immune system plays an increasingly recognized role in the development and propagation of autoimmune liver injury. NKT cells predominantly reside in the liver sinusoids, and through their ability to rapidly produce a wide variety of cytokines (e.g. Th1, TH2, Th17 cytokine patterns), are a critical checkpoint that bridges innate and adaptive immune responses. Specifically, activated NKT cells are capable of transactivating other innate and adaptive immune cells within the liver to amplify and regulate subsequent immune responses within the liver. It has been hypothesized that NKT cells in the setting of autoimmune liver disease can play diverse roles, including driving both anti-inflammatory and proinflammatory responses, as well as regulating the hepatic recruitment of other types of immunoregulatory cells, including regulatory T cells.
自身免疫性肝病主要有三大类，即自身免疫性肝炎（AIH）、原发性胆汁性肝硬化（PBC）和原发性硬化性胆管炎（PSC）。这些疾病的病因仍不完全清楚，但似乎涉及免疫、遗传和环境因素的综合作用。尽管这三种疾病的临床、血清学和组织学特征各不相同，但它们都有共同的免疫介导的肝损伤途径。自身免疫性肝病的发生被认为是由于肝脏内促炎和抗炎免疫反应失衡所致，其中促炎免疫反应上调，抗炎免疫反应下调。现有证据表明，在肝脏内的自身免疫反应中，“自身”抗原由抗原呈递细胞（APCs）呈递，然后直接和/或间接激活肝脏内的 NKT 细胞和其他固有免疫细胞。重要的是，肝脏固有免疫系统在自身免疫性肝损伤的发生和发展中起着越来越被认识的作用。NKT 细胞主要存在于肝窦内，通过其快速产生多种细胞因子（如 Th1、TH2、Th17 细胞因子模式）的能力，成为连接固有免疫和适应性免疫反应的关键检查点。具体而言，激活的 NKT 细胞能够转激活肝脏内的其他固有和适应性免疫细胞，从而放大和调节肝脏内随后的免疫反应。有人假设，在自身免疫性肝病的情况下，NKT 细胞可以发挥多种作用，包括驱动抗炎和促炎反应，以及调节其他类型的免疫调节细胞（如调节性 T 细胞）在肝脏中的募集。
