National-Local Joint Engineering Research Center of Biodiagnosis & Biotherapy, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Shaanxi Provincial Clinical Medical Research Center for Liver and Spleen Diseases, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Front Immunol. 2022 Aug 16;13:941721. doi: 10.3389/fimmu.2022.941721. eCollection 2022.
The liver is a site of complex immune activity. The hepatic immune system tolerates harmless immunogenic loads in homeostasis status, shelters liver function, while maintaining vigilance against possible infectious agents or tissue damage and providing immune surveillance at the same time. Activation of the hepatic immunity is initiated by a diverse repertoire of hepatic resident immune cells as well as non-hematopoietic cells, which can sense "danger signals" and trigger robust immune response. Factors that mediate the regulation of hepatic immunity are elicited not only in liver, but also in other organs, given the dual blood supply of the liver both portal vein blood and arterial blood. Emerging evidence indicates that inter-organ crosstalk between the liver and other organs such as spleen, gut, lung, adipose tissue, and brain is involved in the pathogenesis of liver diseases. In this review, we present the features of hepatic immune regulation, with particular attention to the correlation with factors from extrahepatic organ. We describe the mechanisms by which other organs establish an immune association with the liver and then modulate the hepatic immune response. We discuss their roles and distinct mechanisms in liver homeostasis and pathological conditions from the cellular and molecular perspective, highlighting their potential for liver disease intervention. Moreover, we review the available animal models and methods for revealing the regulatory mechanisms of these extrahepatic factors. With the increasing understanding of the mechanisms by which extrahepatic factors regulate liver immunity, we believe that this will provide promising targets for liver disease therapy.
肝脏是一个复杂的免疫活性部位。在稳态下，肝脏免疫系统耐受无害的免疫原性负荷，保护肝功能，同时保持对可能的感染因子或组织损伤的警惕，并提供免疫监视。肝脏免疫的激活是由多种肝脏固有免疫细胞和非造血细胞启动的，这些细胞可以感知“危险信号”，并引发强烈的免疫反应。介导肝脏免疫调节的因素不仅在肝脏中被引出，而且在其他器官中也被引出，因为肝脏有双重血液供应，门静脉血液和动脉血液。新出现的证据表明，肝脏和其他器官（如脾、肠道、肺、脂肪组织和脑）之间的器官间串扰参与了肝脏疾病的发病机制。在这篇综述中，我们介绍了肝脏免疫调节的特征，特别关注与来自肝外器官的因素的相关性。我们描述了其他器官与肝脏建立免疫联系并调节肝脏免疫反应的机制。我们从细胞和分子的角度讨论了它们在肝脏稳态和病理条件下的作用和独特机制，强调了它们在肝脏疾病干预中的潜力。此外，我们还回顾了现有的动物模型和方法，以揭示这些肝外因素的调节机制。随着对肝外因素调节肝脏免疫的机制的认识不断加深，我们相信这将为肝脏疾病的治疗提供有希望的靶点。
