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 therapeutic approaches.

• Applicants: Professorin Dr. Elke Eggenhofer; Dr. Bettina Proneth
• Subject Area: General and Visceral Surgery
• Term: from 2018 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 406231667

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.

• DFG Programme: Research Grants