单核巨噬细胞是一类重要的天然免疫细胞，在肝脏微环境中大量聚集并在肝脏的炎症反应、组织修复和介导免疫耐受中发挥重要作用。前期研究发现单核巨噬细胞与乙型肝炎病毒（HBV）感染清除及乙型肝炎的发生发展密切相关，但尚不了解HBV感染后如何影响肝脏微环境特别是单核巨噬细胞的免疫特性，以及慢性感染状态下单核巨噬细胞对肝脏微环境的调节作用。本项目拟以单核巨噬细胞为研究肝脏区域免疫特性的细胞代表和切入点,采用规范化的临床标本,结合细胞和小鼠模型,深入研究HBV慢性感染对肝脏内单核巨噬细胞分化和功能的影响及其分子机制，并进一步从细胞间网络调控的角度研究病理微环境下单核巨噬细胞对肝脏中其它免疫细胞的调节作用和机制,解析其与乙肝病程间的动态关系。本研究将有利于加深对肝脏区域免疫特性及肝脏疾病病理机制的认识,为开发相关免疫治疗策略提供靶点和理论基础。

The liver is a complex organ, with a predominant innate immunity, composed of parenchymal cells, nonparenchymal cells, the liver sinusoids, Disse space and the various immunomodulatory factors produced by the cells. As one of the most abundant immune cell type in the liver, monocytes/macrophages are key innate immune cells that reside in the sinusoids. Studies have suggested that liver-resident monocytes/macrophages play an important role of in the development of chronic hepatitis, though the mechanisms involved have not yet been identified. To get insight into the role of monocyte-derived macrophages in changing the immune response in chronically HBV-infected liver microenvironment, this project, employing in vitro & in vivo cellular and animal models as well as human clinical samples, aims to investigate the impact of HBV on the polarization and immunomodulatory functions of liver monocytes/macrophages, analyze the relationships between the distribution and development of various types of macrophages, their impact on the regulation of liver associated immune cells, immune networks and disease progression, and reveal the underlying molecular mechanisms. Collectively, the results of these studies will further increase our understanding of the liver-specialized immunologic features and their interplay with liver diseases and will provide novel targets for immune therapies against liver-associated diseases such as chronic HBV.