The dual role of Fas-ligand as an injury effector and defense strategy in diabetes and islet transplantation

Michal Pearl-Yafe, Esma S. Yolcu, Isaac Yaniv, Jerry Stein, Haval Shirwan, Nadir Askenasy*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

The exact process that leads to the eruption of autoimmune reactions against β cells and the evolution of diabetes is not fully understood. Macrophages and T cells may launch an initial immune reaction against the pancreatic islets of Langerhans, provoking inflammation and destructive insulitis. The information on the molecular mechanisms of the emergence of β cell injury is controversial and points to possibly important roles for the perforin-granzyme, Fas-Fas-ligand (FasL) and tumor-necrosis-factor-mediated apoptotic pathways. FasL has several unique features that make it a potentially ideal immunomodulatory tool. Most important, FasL is selectively toxic to cytotoxic T cells and less harmful to regulatory T cells. This review discusses the intrinsic sensitivity of β cells to FasL-mediated apoptosis, the conditions that underlie this β cell sensitivity, and the feasibility of using FasL to arrest autoimmunity and prevent islet allograft rejection. In both the autoimmune and transplant settings, it is imperative to progress from the administration of nonspecific immunosuppressive therapy to the concept of β-cell-specific immunomodulation. FasL evolves as a prime candidate for antigen-specific immunomodulation.

Original languageEnglish
Pages (from-to)211-222
Number of pages12
JournalBioEssays
Volume28
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

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