Coordination Funds

协调基金

• 批准号: 426581255
• 负责人: Professor Dr. Christoph Schramm
• 金额: --
• 依托单位: I. Medizinische Klinik und Poliklinik
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/426581255?language=en
• 关键词: Coordination; Funds

Primary Sclerosing Cholangitis (PSC) is a relatively rare, chronic progressive disease of bile ducts which leads to liver cirrhosis and cholangiocarcinoma. To date there is no effective therapy to alter the progressive course of disease. Patient survival is limited by the high risk of cirrhosis as well as hepatobiliary malignancy, but in addition health related quality of life is often impaired by PSC-associated complications such as osteoporosis.PSC is characterized by inflammation and fibrosis of intra- and/or extrahepatic bile ducts and by its strong association with inflammatory bowel disease, most often PSC-asssociated pancolitis. These disease features underline the importance of the mucosal surface for disease pathogenesis. In recent years it has become clear that the microbiome is critical for the maintenance and breach of mucosal immune homeostasis. Within the CRU306 we hypothesize that the microbiome and its associated immunological and metabolic changes determine disease pathogenesis and course. In previous work we could show that PSC is associated with changes in intestinal microbiota composition, which were validated across geographical regions, and recently also with changes in the biliary microbiota. We have shown that PSC is associated with altered immune cell populations in blood and liver and that T cells from patients with PSC showed increased pro-inflammatory cytokine production after stimulation with heat-inactivated bacteria. The CRU brings together a number of clinical and basic science experts in hepatology, immunology, microbiome research and bioinformatics. In the next funding period we will focus on the functional meaning of the observed changes in PSC-associated microbiota, immunological and metabolic patterns with regard to disease pathogenesis, phenotype and disease course in humans and respective mouse models.

原发性硬化性胆管炎（PSC）是一种相对罕见的慢性进行性胆管疾病，可导致肝硬化和胆管癌。到目前为止，还没有有效的治疗方法来改变疾病的进展过程。患者的存活率受到肝硬化以及肝胆恶性肿瘤的高风险的限制，但是另外，与健康相关的生活质量通常受到PSC相关并发症如骨质疏松症的损害。PSC的特征在于肝内和/或肝外胆管的炎症和纤维化，以及其与炎性肠病的强烈关联，最常见的是PSC相关的全结肠炎。这些疾病特征强调了粘膜表面对疾病发病机制的重要性。近年来，已经清楚的是，微生物组对于维持和破坏粘膜免疫稳态至关重要。在CRU 306中，我们假设微生物组及其相关的免疫和代谢变化决定了疾病的发病机制和病程。在以前的工作中，我们可以证明PSC与肠道微生物群组成的变化有关，这些变化在不同地理区域得到了验证，最近还与胆汁微生物群的变化有关。我们已经证明PSC与血液和肝脏中改变的免疫细胞群相关，并且PSC患者的T细胞在用热灭活细菌刺激后显示出促炎细胞因子产生增加。CRU汇集了肝病学、免疫学、微生物组研究和生物信息学方面的临床和基础科学专家。在下一个资助期内，我们将专注于观察到的PSC相关微生物群变化的功能意义，免疫和代谢模式与人类和相应小鼠模型中的疾病发病机制，表型和病程有关。