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，并且在细胞间通讯和免疫应答调节中发挥重要作用。本文提出的研究项目将调查外泌体在酒精性脂肪性肝炎（ASH）发病机制中的重要性，这是一种重要的免疫介导的肝脏疾病。为此目的，应表征来自患有ASH的患者的外泌体，以鉴定与该诊断相关的分子外泌体特征。此外，体外和体内（即在患者和动物模型中的相关性研究）应阐明重要代谢因子（ω-3-和ω-6-脂肪酸、维生素D）对外来体含量和功能的潜在影响，这些代谢因子可调节肝脏炎症反应。最后，在ASH动物模型中的体外实验和研究将研究外泌体如何调节对ASH建立至关重要的肝脏先天免疫应答。总的来说，这项研究项目将为理解外泌体的作用及其在ASH发病机制中的关键代谢因素的操纵奠定基础，ASH是一种研究不足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.