- Dr. Jiangping Wu, Principal Investigator
- Notre-Dame Hospital, University of Montreal, Montreal, Canada
- Use of a Death Decoy Protein to Protect Organ Graft from Rejection
Organ transplantation is an effective way to treat various end-stage organ failures. Organ grafts will be rejected by recipients because their immune system will recognize the grafts as foreign entities. Even with administration of immunosuppressive drugs, many grafts are eventually lost due to chronic rejection, which is caused by long-term, low-level immune response and inflammation. During such processes, endothelial cells (EC) and vascular smooth muscle cells (VSMC) around blood vessels are killed, and their death in turn causes a cascade of events that leads to chronic rejection.
A molecule known as death decoy receptor 3 (DcR3/TR6) belongs to the tumor necrosis factor family. Many tumors secrete this molecule to gain survival advantage. DcR3/TR6 can interfere with immune responses and protect many types of cells from death. In this project, we will use the molecule for a good cause. We will investigate whether DcR3/TR6 can ameliorate acute as well as chronic graft rejection. Through genetic engineering, we will let recipient mice secrete high levels of DcR3/TR6 into their blood, or let donor organs produce a large amount of DcR3/TR6 locally. We will then assess whether such manipulation can inhibit activation of the host immune system, reduce death of EC and VSMC, and subsequently reduce acute as well as chronic rejection. The results, if as expected, will prove in principle that this strategy can be used to improve outcome of human organ transplantation.