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

肝脏在耐受和免疫之间起着重要的免疫学作用。失衡会导致慢性感染或自身免疫性疾病，可能导致肝硬化。其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进行操作，以治疗各自的疾病。为此，有必要检查不同的肝细胞亚群，以了解它们的免疫功能。一个相对较新的发现亚群，自然杀伤T细胞，已知参与各种自身免疫性疾病，耐受诱导和抗肿瘤免疫。它们在肝脏疾病中的作用尚不清楚。最近的研究表明，这些自然杀伤T细胞的一个亚型，即I型自然杀伤T细胞，在介导小鼠自身免疫性肝炎方面发挥着关键作用，而另一个亚型，即II型自然杀伤T细胞，能够在激活后保护小鼠免受肝炎的侵袭。在本提案中，应审查这种保护是如何调解的。据推测，II型自然杀伤T细胞的激活导致无能的I型自然杀伤T细胞的招募。将研究肝脏无能诱导和自身抗原呈递的机制，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.