Department of Immunology, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway.
Department of Gastroenterological Surgery, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Hepatology. 2019 Aug;70(2):725-736. doi: 10.1002/hep.30508. Epub 2019 Jul 15.
The liver is both an immunologically complex and a privileged organ. The innate immune system is a central player, in which the complement system emerges as a pivotal part of liver homeostasis, immune responses, and crosstalk with other effector systems in both innate and adaptive immunity. The liver produces the majority of the complement proteins and is the home of important immune cells such as Kupffer cells. Liver immune responses are delicately tuned between tolerance to many antigens flowing in from the alimentary tract, a tolerance that likely makes the liver less prone to rejection than other solid organ transplants, and reaction to local injury, systemic inflammation, and regeneration. Notably, complement is a double-edged sword as activation is detrimental by inducing inflammatory tissue damage in, for example, ischemia-reperfusion injury and transplant rejection yet is beneficial for liver tissue regeneration. Therapeutic complement inhibition is rapidly developing for routine clinical treatment of several diseases. In the liver, targeted inhibition of damaged tissue may be a rational and promising approach to avoid further tissue destruction and simultaneously preserve beneficial effects of complement in areas of proliferation. Here, we argue that complement is a key system to manipulate in the liver in several clinical settings, including liver injury and regeneration after major surgery and preservation of the organ during transplantation.
肝脏既是一个免疫复杂的器官，也是一个具有特权的器官。先天免疫系统是一个核心参与者，其中补体系统作为肝脏内稳态、免疫反应以及与先天和适应性免疫中的其他效应系统相互作用的关键部分出现。肝脏产生大部分补体蛋白，也是重要免疫细胞如枯否细胞的所在地。肝脏免疫反应在耐受来自肠道的许多抗原和对局部损伤、全身炎症和再生的反应之间被精细地调节。值得注意的是，补体是一把双刃剑，因为其激活会通过诱导缺血再灌注损伤和移植排斥等炎症性组织损伤而产生有害作用，但对肝脏组织再生有益。针对补体的治疗性抑制正在迅速发展，以常规治疗几种疾病。在肝脏中，针对受损组织的靶向抑制可能是一种合理且有前途的方法，可以避免进一步的组织破坏，同时保留补体在增殖区域的有益作用。在这里，我们认为补体是几个临床环境中需要操纵的关键系统，包括大手术后的肝脏损伤和再生以及移植过程中对器官的保存。
