Abstract
Abundant information is available on the involvement of various cellular and molecular mechanisms in β cell apoptosis. The experimental evidence is controversial and difficult to reconcile, and the mechanisms of evasion of the autoreactive clones from immune surveillance are poorly understood. Multiple apoptotic pathways play a role in destructive insulitis, including perforin/granzyme, Fas/Fas-ligand (FasL), and other members of the necrosis factor superfamily. These pathways present redundant behaviors in both the initial and late stages of + cell injury, and at the same time, each molecular mechanism is dispensable in the evolution of autoimmune diabetes. There may be a preferential use of perforin/ granzyme in CD8+ T cell-mediated lysis, which participates in onset of autoimmunity, and a predominance of FasL in CD4+ T cell-mediated insulitis. Several cytokines released in the inflammatory infiltrate induce Fas expression in cells, priming them to FasL-mediated apoptosis. In this review, we focus on the possible participation of multiple cell subsets and molecular mechanisms in the pathogenesis of diabetes to the point where inflammation incites an irreversible vicious cycle that perpetuates βcell death.
Keywords: Autoimmune diabetes, βcells, insulitis, T cells, antigen presenting cells, perforin/granzyme, Fas-ligand, tumor necrosis factor
Current Pharmaceutical Design
Title: Pancreatic Islets Under Attack: Cellular and Molecular Effectors
Volume: 13 Issue: 7
Author(s): Michal Pearl-Yafe, Ayelet Kaminitz, Esma S. Yolcu, Isaac Yaniv, Jerry Stein and Nadir Askenasy
Affiliation:
Keywords: Autoimmune diabetes, βcells, insulitis, T cells, antigen presenting cells, perforin/granzyme, Fas-ligand, tumor necrosis factor
Abstract: Abundant information is available on the involvement of various cellular and molecular mechanisms in β cell apoptosis. The experimental evidence is controversial and difficult to reconcile, and the mechanisms of evasion of the autoreactive clones from immune surveillance are poorly understood. Multiple apoptotic pathways play a role in destructive insulitis, including perforin/granzyme, Fas/Fas-ligand (FasL), and other members of the necrosis factor superfamily. These pathways present redundant behaviors in both the initial and late stages of + cell injury, and at the same time, each molecular mechanism is dispensable in the evolution of autoimmune diabetes. There may be a preferential use of perforin/ granzyme in CD8+ T cell-mediated lysis, which participates in onset of autoimmunity, and a predominance of FasL in CD4+ T cell-mediated insulitis. Several cytokines released in the inflammatory infiltrate induce Fas expression in cells, priming them to FasL-mediated apoptosis. In this review, we focus on the possible participation of multiple cell subsets and molecular mechanisms in the pathogenesis of diabetes to the point where inflammation incites an irreversible vicious cycle that perpetuates βcell death.
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Cite this article as:
Pearl-Yafe Michal, Kaminitz Ayelet, Yolcu S. Esma, Yaniv Isaac, Stein Jerry and Askenasy Nadir, Pancreatic Islets Under Attack: Cellular and Molecular Effectors, Current Pharmaceutical Design 2007; 13 (7) . https://dx.doi.org/10.2174/138161207780249155
DOI https://dx.doi.org/10.2174/138161207780249155 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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