In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis.
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.
Siffrin
Volker
V
Neurology Department, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany. siffrinv@gmx.de
Radbruch
Helena
H
Glumm
Robert
R
Niesner
Raluca
R
Paterka
Magdalena
M
Herz
Josephine
J
Leuenberger
Tina
T
Lehmann
Sabrina M
SM
Luenstedt
Sarah
S
Rinnenthal
Jan Leo
JL
Laube
Gregor
G
Luche
Hervé
H
Lehnardt
Seija
S
Fehling
Hans-Joerg
HJ
Griesbeck
Oliver
O
Zipp
Frauke
F
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*
D020381:Interleukin-17; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium