Impact of metabolic factors on exosome-mediated liver inflammation in alcoholic steatohepatitis

外泌体是由几乎所有细胞类型分泌的小膜囊泡，在细胞间通讯和免疫反应调节中起重要作用。本文拟开展的研究项目将探讨外泌体在酒精性脂肪性肝炎（ASH）这一重要的免疫介导的肝脏疾病发病机制中的重要性。为此，应对ASH患者的外泌体进行表征，以确定与此诊断相关的分子外泌体特征。此外，体外和体内（即患者和动物模型的相关性研究）应阐明可调节肝脏炎症反应的重要代谢因子（omega-3和omega-6脂肪酸、维生素D）对外泌体含量和功能的影响。最后，在体外实验和ASH动物模型的研究中，将探讨外泌体如何调节肝脏先天免疫反应，这是建立ASH的关键。总的来说，本研究项目将为了解外泌体及其关键代谢因子在ASH发病机制中的作用奠定基础，ASH是一种尚未得到充分研究但非常重要的免疫介导的肝脏疾病。

Exosomes are small membranous vesicles that are secreted by virtually all cell types and which play an important role in intercellular communication and regulation of immune responses. The here proposed research project shall investigate the importance of exosomes in the pathogenesis of alcoholic steatohepatitis (ASH), an important immune-mediated liver diseases. For this purpose, exosomes from patients with ASH shall be characterized in order to identify molecular exosomal signatures associated with this diagnosis. Furthermore, in vitro and in vivo (i.e. correlation studies in patients and animal models) shall clarify the potential of important metabolic factors (omega-3- and omega-6-fatty acids, vitamin D), which can modulate hepatic inflammatory responses, to impact on the content and function of exosomes. Finally, in vitro experiments and studies in an animal model of ASH shall investigate how exosomes regulate hepatic innate immune responses which are critical for the establishment of ASH. Overall, this research project shall establish the basis of the understanding of the role of exosomes and their manipulation by key metabolic factors in the pathogenesis of ASH, an under-investigated, but highly important immune-mediated liver disease.