Ischemia-Reperfusion Injury in Liver Transplantation: role of the alarmin IL-33 and NKT cells in Humans and in a Mouse model.
Présentation du projet de thèse
Co-directeurs : A. Herbelin, E. Salamé
The interleukin 33 (IL-33) belongs to the IL-1 superfamily and is constitutively expressed in normal tissues. IL-33 can act as an endogenous danger signal when produced in largest amount during endothelial or epithelial cellular injuries. IL-33 may play at the same time the role of an alarmin (cytokine that signals danger) and the role of a transcription factor, contributing to the activation of the adaptive immune system. ST2/IL-1RAcP is the receptor for IL-33, ST2 being either membranous or soluble. Liver graft ischemia-reperfusion injuries result from a dynamic process involving ischemia, when the graft is stored in a 4°C preservation solution, and reperfusion, when the graft is re-vascularized in the recipient. NKT cells play a role in the early phase but also in the late phase of ischemia-reperfusion, and participate in the activation of the adaptive immune response.
The aim of my PhD is to study the role of IL-33 and NKT cells in liver graft ischemia-reperfusion in different conditions:
- In Humans, with the creation of a blood samples bank in liver transplant recipients from Tours transplantation center,
- In Mice, with a model of warm ischemia and eventually the development of a model of liver transplantation.
Endpoints will be:
- Histology: ischemia-reperfusion injuries in liver samples or biopsies
- Liver function tests assessing graft function: AST, ALT, bilirubinemia, prothrombin time
- Serum IL-33 and sST2, activation of NK and NKT cells, serum and intracellular cytokines.