Die Rolle von natürlichen Killer T Zellen in entzündlicher Lebererkrankung: Untersuchung des Schutzmechanismus vor Concanavalin-A induzierter Hepatitis

肝脏在机体耐受和免疫之间起着重要的免疫作用。失衡会导致慢性感染或自身免疫性疾病，从而导致肝硬化。目的是获得控制这种平衡的知识，并朝着一个或另一个方向操纵，以治疗各自的疾病。为此，检查不同的肝细胞亚群是必要的，以了解他们的免疫功能。一个相对较新发现的亚群，自然杀伤T细胞，已知参与多种自身免疫性疾病，耐受性诱导和抗肿瘤免疫。它们在肝脏疾病中的作用尚不清楚。最近有研究表明，这些自然杀伤T细胞的一种亚型，即I型自然杀伤T细胞，在介导小鼠自身免疫性肝炎中起着关键作用，而另一种亚型，即II型自然杀伤T细胞，在激活后能够保护小鼠免受肝炎的侵袭。在本提案中，应审查如何调解这种保护。据推测，II型自然杀伤T细胞的激活导致无能I型自然杀伤T细胞的募集。肝脏的能量诱导和自身抗原呈递机制将被研究以寻找潜在的治疗靶点。

The liver plays an important immunological role between tolerance and immunity. Dysbalance results in chronic infection or autoimmune disease, capable of leading to liver cirrhosis. The aim is to achieve the knowledge to control this balance and manipulate towards one or the other direction in order to treat the respective disease. For this, examination of the different liver cell subsets is necessary to understand their immunological functions. A relatively new discovered subset, the natural killer T cells, is known to be involved in diverse autoimmune diseases, tolerance induction and in anti-tumor immunity. Their role in liver diseases is not yet understood. It has recently been shown that a subtype of these natural killer T cells, type I natural killer T cells, plays a critical role in mediating autoimmune hepatitis in mice, while another subtype, type II natural killer T cells, is able to protect mice from hepatitis upon activation. In this proposal, it shall be examined, how this protection is mediated. It is hypothesized, that activation of type II natural killer T cells leads to recruitment of anergic type I natural killer T cells. Mechanisms of anergy induction and self-antigenpresentation in the liver will be investigated to find potential therapeutic targets.