Related Experiment Video
Updated: Sep 20, 2026
A Method for Murine Islet Isolation and Subcapsular Kidney Transplantation
Published on: April 13, 2011
DcR3/TR6 effectively prevents islet primary nonfunction after transplantation
Yulian Wu1, Bing Han, Hongyu Luo
1Laboratory of Transplantation Immunology, Centre hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada.
Abstract:
Islet primary nonfunction (PNF) is defined as the loss of islet function after transplantation for reasons other than graft rejection. It is a major obstacle to successful and efficient islet transplantation. DcR3/TR6 is a soluble death decoy receptor belonging to the tumor necrosis factor (TNF) receptor family, and it can block apoptosis mediated by several TNF receptor family members such as Fas and LT beta R. In this study, we used TR6 to protect islets from PNF after transplantation. Untreated isogeneic or allogeneic islet transplantation had PNF incidence of 25 and 26.5%, respectively. Administration of TR6 totally prevented PNF in allogeneic islet transplantation. In vitro experiments showed an increased apoptosis among islets that were treated with FasL and gamma-interferon (IFN-gamma) in combination. TR6 significantly reduced such apoptosis. Functional study showed that insulin release was compromised after FasL and IFN-gamma treatment, and the compromise could be prevented with TR6-Fc. This indicates that TR6 indeed protected beta-cells from damage caused by FasL and IFN-gamma. Further in vivo experiments showed that syngeneic islet transplantation between lpr/lpr and gld/gld mice was significantly more efficacious than that conducted between wild-type mice. These results suggest that Fas-mediated apoptosis plays an important role in PNF, and use of TR6 may be a novel strategy to prevent PNF in clinical islet transplantation.
Insights
Primary nonfunction (PNF) of transplanted islets, a major obstacle, can be prevented. The study shows that TR6, a decoy receptor, protects islets from Fas-mediated apoptosis, suggesting a novel strategy for clinical islet transplantation.
Area of Science:
- Immunology
- Transplantation Biology
- Cell Death Pathways
Background:
- Primary nonfunction (PNF) is a significant barrier to successful islet transplantation.
- DcR3/TR6 is a soluble decoy receptor that inhibits apoptosis mediated by tumor necrosis factor (TNF) receptor family members.
- Fas-mediated apoptosis is implicated in PNF.
Purpose of the Study:
- To investigate the potential of TR6 in preventing PNF after islet transplantation.
- To elucidate the role of Fas-mediated apoptosis in PNF.
- To evaluate TR6 as a therapeutic strategy for PNF.
Main Methods:
- Islet transplantation in syngeneic and allogeneic models.
- In vitro treatment of islets with FasL and IFN-gamma, with and without TR6.
- Assessment of apoptosis and insulin release.
- In vivo experiments using Fas-deficient mice (lpr/lpr and gld/gld).
Main Results:
- Untreated islet transplantation showed PNF rates of 25% (isogeneic) and 26.5% (allogeneic).
- TR6 administration completely prevented PNF in allogeneic transplantation.
- TR6 significantly reduced FasL and IFN-gamma-induced islet apoptosis and preserved insulin release.
- Syngeneic islet transplantation in Fas-deficient mice was more effective than in wild-type mice.
Conclusions:
- Fas-mediated apoptosis plays a critical role in islet primary nonfunction.
- TR6 effectively protects beta-cells from FasL and IFN-gamma-induced damage.
- TR6 represents a promising novel therapeutic strategy to prevent PNF in clinical islet transplantation.
