Impact of chronic IFN-I signalling in liver fibrosis on anti-viral immunity ((2)-P32*)

肝纤维化患者对病毒和细菌感染易感性增强的潜在细胞和分子因素尚不清楚。最近，我们在初步实验中发现肠道微生物群的易位诱导慢性IFN-I表达，从而阻碍病毒清除。在这个项目中，我们的目标是探索IFN-I可能影响肝纤维化中抗病毒免疫关键参与者（即抗原提呈细胞、CD4 T和CD8 T细胞）功能的细胞和分子机制，以及这可能如何延续和加速纤维化过程。该项目的结果将增强我们对肝纤维化患者细胞免疫受损、持续感染导致肝纤维化加重的理解，并可能为治疗和疫苗接种方法开辟新的领域。

The underlying cellular and molecular factors for the enhanced susceptibility of patients with liver fibrosis to viral and bacterial infections are unclear. Recently, we found that translocation of gut microbiota induces chronic IFN-I expression, which hampers viral clearance in a preliminary experiments. In this project, we aim to explore the cellular and molecular mechanisms by which IFN-I might affect the function of key players of anti-viral immunity i.e. antigen presenting cells, CD4 T and CD8 T cells in liver fibrosis and how this may perpetuate and accelerate the fibrogenic process. The results of this project will enhance our understanding of impaired cellular immunity in patients with liver fibrosis, aggravation of liver fibrosis by persistent infection and potentially open new venues for therapeutic and vaccination approaches.