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          Institute: MPI für Neurobiologie     Collection: Systems and Computational Neurobiology     Display Documents

ID: 508159.0, MPI für Neurobiologie / Systems and Computational Neurobiology
In Vivo Imaging of Partially Reversible Th17 Cell-Induced Neuronal Dysfunction in the Course of Encephalomyelitis
Authors:Siffrin, V.; Radbruch, H.; Glumm, R.; Niesner, R.; Paterka, M.; Herz, J.; Leuenberger, T.; Lehmann, S. M.; Luenstedt, S.; Rinnenthal, J. L.; Laube, G.; Luche, H.; Lehnardt, S.; Fehling, H. J.; Griesbeck, O.; Zipp, F.
Date of Publication (YYYY-MM-DD):2010-09-24
Title of Journal:Immunity
Journal Abbrev.:Immunity
Issue / Number:3
Start Page:424
End Page:436
Review Status:Peer-review
Audience:Not Specified
Abstract / Description: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 Ca2+ 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.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Affiliations:MPI für Neurobiologie/Systems and Computational Neurobiology (Borst)/Cellular Dynamics (Griesbeck)
External Affiliations:[Siffrin, Volker; Zipp, Frauke] Johannes Gutenberg Univ Mainz, Univ Med Ctr Mainz, Dept Neurol, D-55131 Mainz, Germany.; [Siffrin, Volker; Radbruch, Helena; Glumm, Robert; Niesner, Raluca; Paterka, Magdalena; Herz, Josephine; Leuenberger, Tina; Luenstedt, Sarah; Rinnenthal, Jan Leo; Zipp, Frauke] Max Delbruck Ctr Mol Med Berlin Buch, D-13125 Berlin, Germany.; [Radbruch, Helena; Glumm, Robert; Niesner, Raluca; Herz, Josephine; Luenstedt, Sarah] Charite Univ Med Ctr Berlin, D-10117 Berlin, Germany.; [Lehmann, Sabrina M.; Laube, Gregor; Lehnardt, Seija] Charite, Inst Cell Biol & Neurobiol, D-10117 Berlin, Germany.; [Luche, Herve; Fehling, Hans-Joerg] Univ Clin Ulm, Inst Immunol, D-89081 Ulm, Germany.
Identifiers:ISI:000282798500016 [ID No:1]
ISSN:1074-7613 [ID No:2]
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