Molecular mechanisms of death ligand‐mediated immune modulation: A gene therapy model to prolong islet survival in type 1 diabetes
- 4 February 2008
- journal article
- review article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 104 (3), 710-720
- https://doi.org/10.1002/jcb.21677
Abstract
Type 1 diabetes results from the T cell‐mediated destruction of pancreatic beta cells. Islet transplantation has recently become a potential therapeutic approach for patients with type 1 diabetes. However, islet‐graft failure appears to be a challenging issue to overcome. Thus, complementary gene therapy strategies are needed to improve the islet‐graft survival following transplantation. Immune modulation through gene therapy represents a novel way of attacking cytotoxic T cells targeting pancreatic islets. Various death ligands of the TNF family such as FasL, TNF, and TNF‐Related Apoptosis‐Inducing Ligand (TRAIL) have been studied for this purpose. The over‐expression of TNF or FasL in pancreatic islets exacerbates the onset of type 1 diabetes generating lymphocyte infiltrates responsible for the inflammation. Conversely, the lack of TRAIL expression results in higher degree of islet inflammation in the pancreas. In addition, blocking of TRAIL function using soluble TRAIL receptors facilitates the onset of diabetes. These results suggested that contrary to what was observed with TNF or FasL, adenovirus mediated TRAIL gene delivery into pancreatic islets is expected to be therapeutically beneficial in the setting of experimental models of type 1 diabetes. In conclusion; this study mainly reveals the fundamental principles of death ligand‐mediated immune evasion in diabetes mellitus. J. Cell. Biochem. 104: 710–720, 2008.Keywords
This publication has 74 references indexed in Scilit:
- CCL4 Protects From Type 1 Diabetes by Altering Islet β-Cell–Targeted Inflammatory ResponsesDiabetes, 2007
- NF-κB prevents β cell death and autoimmune diabetes in NOD miceProceedings of the National Academy of Sciences of the United States of America, 2007
- Pleiotropic functions of TNF-α determine distinct IKKβ-dependent hepatocellular fates in response to LPSAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2007
- Gene therapy for diabetes: reinventing the isletTrends in Endocrinology & Metabolism, 2006
- Therapeutic gene causing lymphomaNature, 2006
- Synergistic inhibition of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human pancreatic β cells by Bcl-2 and X-linked inhibitor of apoptosisHuman Immunology, 2005
- Transplantation of islets transduced with CTLA4-Ig and TGFβ using adenovirus and lentivirus vectorsTransplant Immunology, 2004
- In VivoGene Transfer to Pancreatic Beta Cells by Systemic Delivery of Adenoviral VectorsHuman Gene Therapy, 2004
- Local Expression of TNFα in Neonatal NOD Mice Promotes Diabetes by Enhancing Presentation of Islet AntigensImmunity, 1998
- The Novel Receptor TRAIL-R4 Induces NF-κB and Protects against TRAIL-Mediated Apoptosis, yet Retains an Incomplete Death DomainImmunity, 1997