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

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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.