Robinson Mark W, Harmon Cathal, O'Farrelly Cliona
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin D2, Ireland.
School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin D2, Ireland.
Cell Mol Immunol. 2016 May;13(3):267-76. doi: 10.1038/cmi.2016.3. Epub 2016 Apr 11.
The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the non-diseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear 'dangerous' stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease.
人类肝脏通常被视为主要参与代谢、营养储存和解毒活动的非免疫器官。然而，我们现在知道，健康的肝脏也是一个由多种免疫细胞以及非造血细胞群体介导的复杂免疫活动场所。在未患病的肝脏中，代谢和组织重塑功能需要炎症成分。这种炎症，再加上经常接触饮食和微生物产物，会产生过度免疫激活的可能性。在这个复杂的微环境中，肝脏免疫系统耐受无害分子，同时对可能的病原体、恶性细胞或组织损伤保持警惕。在受到病原体或组织损伤的适当免疫激活后，解决炎症的机制对于维持肝脏内环境稳定至关重要。未能清除“危险”刺激或适当调节激活的免疫机制会导致病理性炎症和组织内环境稳定破坏，其特征是纤维化、肝硬化和最终肝功能衰竭的逐步发展。因此，肝脏炎症机制在健康的成年肝脏中具有一系列作用；它们对于维持组织和器官内环境稳定至关重要，而当失调时，是与慢性感染、自身免疫和恶性肿瘤相关的肝脏病理的关键驱动因素。在这篇综述中，我们探讨了正常肝脏内环境稳定中炎症和炎症介质观念的变化，并提出将肝脏特异性免疫调节途径作为治疗肝脏疾病的一种治疗方法。
