Loading...
Neuroprotective intervention by interferon-γ blockade prevents CD8+ T cell-mediated dendrite and synapse loss.
Kreutzfeldt, Mario Bergthaler, Andreas Fernandez, Marylise Brück, Wolfgang Steinbach, Karin Vorm, Mariann Coras, Roland Blümcke, Ingmar Bonilla, Weldy V Fleige, Anne
Kreutzfeldt, Mario
Bergthaler, Andreas
Fernandez, Marylise
Brück, Wolfgang
Steinbach, Karin
Vorm, Mariann
Coras, Roland
Blümcke, Ingmar
Bonilla, Weldy V
Fleige, Anne
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2013-09-23
Submitted date
Files
Loading...
allowed publisher's PDF
Adobe PDF, 4.67 MB
Other Titles
Abstract
Neurons are postmitotic and thus irreplaceable cells of the central nervous system (CNS). Accordingly, CNS inflammation with resulting neuronal damage can have devastating consequences. We investigated molecular mediators and structural consequences of CD8(+) T lymphocyte (CTL) attack on neurons in vivo. In a viral encephalitis model in mice, disease depended on CTL-derived interferon-γ (IFN-γ) and neuronal IFN-γ signaling. Downstream STAT1 phosphorylation and nuclear translocation in neurons were associated with dendrite and synapse loss (deafferentation). Analogous molecular and structural alterations were also found in human Rasmussen encephalitis, a CTL-mediated human autoimmune disorder of the CNS. Importantly, therapeutic intervention by IFN-γ blocking antibody prevented neuronal deafferentation and clinical disease without reducing CTL responses or CNS infiltration. These findings identify neuronal IFN-γ signaling as a novel target for neuroprotective interventions in CTL-mediated CNS disease.
Citation
Neuroprotective intervention by interferon-γ blockade prevents CD8+ T cell-mediated dendrite and synapse loss. 2013, 210 (10):2087-103 J. Exp. Med.
Publisher
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
1540-9538
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
License
Archived with thanks to The Journal of experimental medicine