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Pancreatic Islets Under Attack: Cellular and Molecular Effectors
- Source :
- Current Pharmaceutical Design. 13:749-760
- Publication Year :
- 2007
- Publisher :
- Bentham Science Publishers Ltd., 2007.
-
Abstract
- Abundant information is available on the involvement of various cellular and molecular mechanisms in beta 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 beta 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 beta 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 beta cell death.
- Subjects :
- CD4-Positive T-Lymphocytes
Fas Ligand Protein
Antigen-Presenting Cells
Apoptosis
CD8-Positive T-Lymphocytes
medicine.disease_cause
Fas ligand
Autoimmunity
Islets of Langerhans
Drug Discovery
medicine
Animals
Humans
Antigen-presenting cell
Pharmacology
biology
Macrophages
medicine.disease
Diabetes Mellitus, Type 1
Perforin
Granzyme
Immunology
biology.protein
Cancer research
Tumor necrosis factor alpha
Insulitis
CD8
Subjects
Details
- ISSN :
- 13816128
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- Current Pharmaceutical Design
- Accession number :
- edsair.doi.dedup.....9c9fbf00d3410690ec65d481eefb8a76