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| Item Type: | Article |
|---|---|
| Title: | Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL |
| Creators Name: | Aktas, O., Smorodchenko, A., Brocke, S., Infante-Duarte, C., Schulze Topphoff, U., Vogt, J., Prozorovski, T., Meier, S., Osmanova, V., Pohl, E., Bechmann, I., Nitsch, R. and Zipp, F. |
| Abstract: | Here, we provide evidence for a detrimental role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in neural death in T cell-induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Clinical severity and neuronal apoptosis in brainstem motor areas were substantially reduced upon brain-specific blockade of TRAIL after induction of EAE through adoptive transfer of encephalitogenic T cells. Furthermore, TRAIL-deficient myelin-specific lymphocytes showed reduced encephalitogenicity when transferred to wild-type mice. Conversely, intracerebral delivery of TRAIL to animals with EAE increased clinical deficits, while naive mice were not susceptible to TRAIL. Using organotypic slice cultures as a model for living brain tissue, we found that neurons were susceptible to TRAIL-mediated injury induced by encephalitogenic T cells. Thus, in addition to its known immunoregulatory effects, the death ligand TRAIL contributes to neural damage in the inflamed brain. |
| Keywords: | Adoptive Transfer, Apoptosis, Apoptosis Regulatory Proteins, Western Blotting, Animal Disease Models, Experimental Autoimmune Encephalomyelitis , Flow Cytometry, Immunohistochemistry, Membrane Glycoproteins, Multiple Sclerosis, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor-alpha, Animals, Mice |
| Source: | Neuron |
| ISSN: | 0896-6273 |
| Publisher: | Cell Press |
| Volume: | 46 |
| Number: | 3 |
| Page Range: | 421-432 |
| Date: | 5 May 2005 |
| Additional Information: | The original publication is available at www.sciencedirect.com |
| Official Publication: | https://doi.org/10.1016/j.neuron.2005.03.018 |
| PubMed: | View item in PubMed |
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