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Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL

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Item Type:Article
Title:Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL
Creators Name:Aktas, O. and Smorodchenko, A. and Brocke, S. and Infante-Duarte, C. and Schulze Topphoff, U. and Vogt, J. and Prozorovski, T. and Meier, S. and Osmanova, V. and Pohl, E. and Bechmann, I. and 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
Publisher:Cell Press
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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