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.

检查免疫系统与肝移植中缺血-再灌注损伤方面的受调节坏死事件之间的相互作用，作为开发新治疗方法的基础。

• 批准号: 406231667
• 负责人: Privatdozentin Dr. Elke Eggenhofer
• 金额: --
• 依托单位: Klinik und Poliklinik für Chirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/406231667?language=en
• 关键词: Examination; interaction; between; immune; system

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.

每种器官移植一方面面临器官的排斥反应，另一方面面临缺血-再灌注（= IRI，缺血再灌注损伤）对器官的损伤。在10- 20%的病例中，这种损伤导致器官功能受损和早期移植物衰竭。考虑到目前器官短缺，这是一个严重的临床问题。长期以来，人们认为缺血再灌注是一种无菌性炎症。尽管如此，最近的研究结果表明，先天免疫系统的细胞参与了IRI的发展。产生IL-17的γ-δ T细胞作为一种重要的效应细胞群，在本实验室已被鉴定并发表。此外，我们和其他人最近能够发现，调节性坏死（RN）对肝脏和肾脏的IRI有显著影响，并且这种影响可以通过施用RN的特异性抑制剂来抑制。然而，目前还不完全清楚免疫细胞和正在发生的调节性坏死是如何相互作用的，这是目前还不可能开发特异性IRI治疗的主要原因。对于这个项目，两位科学家PD博士Elke Eggenhofer（大学医院里根斯堡）和博士Bettina Proneth（亥姆霍兹研究所慕尼黑）决定合作，以首先阐明免疫细胞和RN事件的特定相互作用，并开发靶向治疗。Eggenhofers博士的专长是肝脏IRI以及免疫效应细胞的鉴定和表征，而Proneth博士是调节性坏死细胞死亡事件和化学物质干预领域的知名专家。第一个联合初步工作已经发表在《自然细胞生物学》杂志上。