State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University. Hangzhou, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University. Hangzhou, China.
Life Sci. 2020 Jan 1;240:117094. doi: 10.1016/j.lfs.2019.117094. Epub 2019 Nov 21.
The liver serves as a central participant in immune system owing to its particular blood supply and large amounts of immune cells, in which macrophages play a significant role in liver homeostasis and disorders. Extracellular vesicles (EVs), membrane-defined nanometer-sized vesicles released by cells in a tightly controlled manner, have attracted intensive research attention as a critical vehicle for cell-cell communication in the pathophysiology of liver. Accumulating evidence has proved that extracellular vesicles are frequently involved in macrophage-mediated biological behaviors. Not only can macrophages produce and secrete EVs containing multifarious cargo themselves to exert immunomodulatory functions, but also macrophages may serve as target cells of EVs from other cells eliciting the alteration of their phenotype and function. Since both macrophage as well as EVs show pleiotropic and central effects in the progression of liver diseases, their roles in adjusting innate immunity of liver often present a crossover. In this review we are dedicated to deciphering the complex immunological network constituted by macrophages and EVs in several common liver diseases, including acute liver injury or failure and a set of chronic liver diseases such as viral hepatitis B and C, metabolic and alcoholic liver diseases, as well as hepatocellular carcinoma (HCC). From the aspect of immunology, we integrate the mechanism of EVs and hepatic macrophages in the setting of liver diseases and show a promising significance of utilizing this association into clinical immunotherapy.
肝脏因其独特的血液供应和大量的免疫细胞，成为免疫系统的核心参与者，其中巨噬细胞在肝脏稳态和疾病中发挥着重要作用。细胞以严格控制的方式释放的膜定义的纳米大小的囊泡——细胞外囊泡（EVs），作为细胞间通讯的关键载体，在肝脏的病理生理学中引起了广泛的研究关注。越来越多的证据证明细胞外囊泡经常参与巨噬细胞介导的生物学行为。巨噬细胞不仅可以产生和分泌含有多种货物的 EVs 来发挥免疫调节功能，而且巨噬细胞还可以作为来自其他细胞的 EVs 的靶细胞，引起其表型和功能的改变。由于巨噬细胞和 EVs 在肝脏疾病的进展中都表现出多效性和核心作用，它们在调节肝脏固有免疫中的作用经常出现交叉。在这篇综述中，我们致力于破译巨噬细胞和 EVs 在几种常见肝脏疾病（包括急性肝损伤或衰竭和一系列慢性肝脏疾病，如乙型和丙型病毒性肝炎、代谢性和酒精性肝病以及肝细胞癌（HCC））中构成的复杂免疫网络。从免疫学的角度来看，我们整合了 EVs 和肝巨噬细胞在肝脏疾病中的作用机制，并展示了利用这种关联进行临床免疫治疗的有希望的意义。
