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Type of publication: Journal Article
Type of document: Full Paper

Year: 2005

Authors: 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; Zipp, F

Title: Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL.

Source: Neuron. 2005; 46(3):421-432



Authors Vetmeduni Vienna:

Pohl Elena
Smorodchenko Alina


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 Pubmed: Adoptive Transfer
Animals
Apoptosis/immunology
Apoptosis Regulatory Proteins
Blotting, Western
Brain/immunology
Brain/metabolism
Brain/pathology*
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental/immunology
Encephalomyelitis, Autoimmune, Experimental/pathology*
Female
Flow Cytometry
Immunohistochemistry
Membrane Glycoproteins/metabolism*
Mice
Multiple Sclerosis
Neurons/immunology
Neurons/pathology*
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes/immunology
T-Lymphocytes/metabolism*
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha/metabolism*


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