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In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis

Item Type:Article
Title:In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis
Creators Name:Siffrin, V. and Radbruch, H. and Glumm, R. and Niesner, R. and Paterka, M. and Herz, J. and Leuenberger, T. and Lehmann, S.M. and Luenstedt, S. and Rinnenthal, J.L. and Laube, G. and Luche, H. and Lehnardt, S. and Fehling, H.J. and Griesbeck, O. and Zipp, F.
Abstract:Neuronal damage in autoimmune neuroinflammation is the correlate for long-term disability in multiple sclerosis (MS) patients. Here, we investigated the role of immune cells in neuronal damage processes in animal models of MS by monitoring experimental autoimmune encephalomyelitis (EAE) by using two-photon microscopy of living anaesthetized mice. In the brainstem, we detected sustained interaction between immune and neuronal cells, particularly during disease peak. Direct interaction of myelin oligodendrocyte glycoprotein (MOG)-specific Th17 and neuronal cells in demyelinating lesions was associated with extensive axonal damage. By combining confocal, electron, and intravital microscopy, we showed that these contacts remarkably resembled immune synapses or kinapses, albeit with the absence of potential T cell receptor engagement. Th17 cells induced severe, localized, and partially reversible fluctuation in neuronal intracellular Ca(2+) concentration as an early sign of neuronal damage. These results highlight the central role of the Th17 cell effector phenotype for neuronal dysfunction in chronic neuroinflammation.
Keywords:Apoptosis, Axons, Calcium, Cell Communication, Cell Movement, Cultured Cells, Autoimmune, Experimental Encephalomyelitis, Interleukin-17, Neurons, N-Methyl-D-Aspartate Receptors, Synapses, Helper-Inducer T-Lymphocytes, Animals, Mice
Source:Immunity
ISSN:1074-7613
Publisher:Cell Press (U.S.A.)
Volume:33
Number:3
Page Range:424-436
Date:24 September 2010
Official Publication:https://doi.org/10.1016/j.immuni.2010.08.018
PubMed:View item in PubMed

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