title: In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis.
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.
authors.affiliation: Neurology Department, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany. siffrinv@gmx.de
authors.forename: Volker
authors.initials: V
authors.lastname: Siffrin
authors.forename: Helena
authors.initials: H
authors.lastname: Radbruch
authors.forename: Robert
authors.initials: R
authors.lastname: Glumm
authors.forename: Raluca
authors.initials: R
authors.lastname: Niesner
authors.forename: Magdalena
authors.initials: M
authors.lastname: Paterka
authors.forename: Josephine
authors.initials: J
authors.lastname: Herz
authors.forename: Tina
authors.initials: T
authors.lastname: Leuenberger
authors.forename: Sabrina M
authors.initials: SM
authors.lastname: Lehmann
authors.forename: Sarah
authors.initials: S
authors.lastname: Luenstedt
authors.forename: Jan Leo
authors.initials: JL
authors.lastname: Rinnenthal
authors.forename: Gregor
authors.initials: G
authors.lastname: Laube
authors.forename: Hervé
authors.initials: H
authors.lastname: Luche
authors.forename: Seija
authors.initials: S
authors.lastname: Lehnardt
authors.forename: Hans-Joerg
authors.initials: HJ
authors.lastname: Fehling
authors.forename: Oliver
authors.initials: O
authors.lastname: Griesbeck
authors.forename: Frauke
authors.initials: F
authors.lastname: Zipp
mesh_terms: D000818:Animals; D017209:Apoptosis; D001369:Axons / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D002465:Cell Movement; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D020381:Interleukin-17 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
chemical_list: D020381:Interleukin-17; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium