中文摘要
巨噬细胞是肝脏中占比最高的免疫细胞,在肝脏免疫稳态的维持与重塑中,发挥关键调控作用。肝脏巨噬细胞在分化、表型及功能多方面所呈现的复杂异质性影响肝脏的生理状态与疾病发生发展,但是该方面的研究尚留存大量空白。本项目拟基于前期工作结果,以肝脏中高表达B7-DC的巨噬细胞功能群(简称:B7-DChigh巨噬细胞)为研究对象,从解析其在响应炎性信号时,细胞膜表面B7-DC表达水平提高的意义入手,建立B7-DC与巨噬细胞呈现特定免疫特性之间的确切关联;完成B7-DChigh巨噬细胞起源、表型特征、功能的分析,在此基础上,建立巨噬细胞与肝脏炎症之间的新型联结关系;运用新结构药源分子,开展靶向干预B7-DC介导的巨噬细胞炎性,以改善肝脏炎症的尝试。研究结果有助于拓展对巨噬细胞异质性的了解,发现巨噬细胞在调控肝脏炎性微环境稳态中新的响应方式,获取新结构药源分子相关信息,为肝脏炎症的治疗提供新的实验数据。
英文摘要
Macrophages account for the majority of immune cells in liver and play a key regulatory role in immune homeostasis. Complex heterogeneity in differentiation, phenotype and function featured by hepatic macrophages profoundly influences liver physiological state, disease pathogenesis and prognosis. The conceptual nature of the significance merits continuing studies in this field, where it still remains largely unexplored. As an extension of our previous work, we set out to focus on B7-DC highly expressed hepatic macrophage population (abbrev. B7-DChigh macrophages). We seek to first delineate the significance of aberrant overexpression of B7-DC on macrophage membrane in response to inflammatory stimulation. Thereby, to establish accurate relationship of B7-DC to certain immunological characteristics of macrophages and to complete analysis of B7-DChigh macrophages’ origin, phenotypical trait and function. On this basis, novel correlation of macrophages to hepatic inflammation will be established. At the meantime, we will also attempt to ameliorate hepatic inflammation by using novel structural molecules which are able to exert their targeted intervention effects for dysregulated function of hepatic macrophages mediated by B7-DC. Our project will help expand understanding of the heterogeneity of macrophages, discover their unique patterns as response to inflammatory microenvironment and obtain invaluable perspectives on the molecular structure of new drug. Herein, original experimental data on treatment of hepatic inflammation will be provided.
