Examination of the interaction between the immune system and regulated necrotic events in terms of ischemia - reperfusion injury in liver transplantation as a basis for the development of new therapeuticapproaches.

每一个器官移植一方面面临着器官的排斥反应，另一方面又面临着器官的缺血再灌注损伤(=IRI，缺血再灌注损伤)。在10-20%的病例中，这种损伤会导致器官功能受损和早期移植失败。考虑到目前器官短缺，这是一个严重的临床问题。很长一段时间以来，人们认为缺血再灌注是一种无菌炎症。尽管如此，最近的发现表明，先天性免疫系统的细胞参与了IRI的发展。作为一种重要的效应细胞群，产生非常规白细胞介素17的γ-Delta T细胞已在本实验室发现并发表。此外，我们和其他人最近发现，调节性坏死(RN)对肝脏和肾脏的IRI有重要作用，这种作用可以通过给予RN的特定抑制剂来抑制。然而，目前还不完全清楚免疫细胞和正在发生的受调控的坏死是如何相互作用的，这是为什么还不可能开发特定的IRI疗法的主要原因。在这个项目中，两位科学家Elke Eggenhofer博士(雷根斯堡大学医院)和Bettina Proneth博士(慕尼黑Helmholtz研究所)决定合作，以便首先阐明免疫细胞和RN事件的特定相互作用，并开发有针对性的治疗方法。Eggenhofers博士的专长是肝脏IRI以及免疫效应细胞的识别和表征，而Proneth博士是受调控的坏死细胞死亡事件和化学物质干预领域的知名专家。第一个联合的初步工作已经发表在《自然细胞生物学》杂志上。

Each organ transplantation is faced with the rejection of the organ on the hand and with the damage to the organ by ischemia-reperfusion (= IRI , ischemia reperfusion injury ) on the other hand. In 10-20 % of cases this damage leads to impairment of organ function and an early graft failure. This is a serious clinical problem, considering the current shortage of organs. For a long time it was assumed that ischemiareperfusion is a sterile inflammation. Nonetheless recent findings have shown that cells of the innate immune system are involved in the development of the IRI. As one important effector cell population the unconventional interleukine 17 producing gamma-delta T cell could beidentified and published in our lab. In addition, we and others were able to discover recently that the regulated necrosis (RN) contributes significantly to the IRI in the liver and kidney, and that this effect can be inhibited by administration of specific inhibitors of the RN. However, it is not yet entirely clear how the immune cells and theoccurring regulated necrosis interact, which is the main reason why the development of a specific IRI therapy is not yet possible. For this project, the two scientists PD Dr. Elke Eggenhofer (University Hospital Regensburg) and Dr. Bettina Proneth (Helmholtz Institute Munich) decided to cooperate in order to first clarify the specific interaction ofimmune cells and RN events and to develop a targeted therapy. Dr. Eggenhofers expertise is hepatic IRI as well as the identification and characterization of immune effector cells, while Dr. Proneth is a renowned specialist in the field of regulated necrotic cell death events and the intervention of this by chemical substances. The first jointpreliminary work is already published in a Nature Cell Biology publication.