Neuroprotective intervention by interferon-γ blockade prevents CD8+ T cell-mediated dendrite and synapse loss

Kreutzfeldt M, Bergthaler A, Fernandez M, Brueck W, Steinbach K, Vorm M, Coras R, Blümcke I, Bonilla WV, Fleige A, Forman R, Mueller W, Becher B, Misgeld T, Kerschensteiner M, Pinschewer DD, Merkler D (2013)

Publication Type: Journal article

Publication year: 2013

Journal

Journal of Experimental Medicine Rockefeller University Press

Book Volume: 210

Pages Range: 2087-2103

Journal Issue: 10

DOI: 10.1084/jem.20122143

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. © 2013 Kreutzfeldt et al.

Authors with CRIS profile

Roland Coras Institute of Neuropathology Ingmar Blümcke Lehrstuhl für Neuropathologie

Involved external institutions

Georg-August-Universität Göttingen DE Germany (DE) University of Manchester GB United Kingdom (GB) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) University of Geneva / Université de Genève (UNIGE) CH Switzerland (CH) University of Zurich / Universität Zürich (UZH) CH Switzerland (CH) Technische Universität München (TUM) DE Germany (DE) Technische Universität Braunschweig DE Germany (DE)

How to cite

APA:

Kreutzfeldt, M., Bergthaler, A., Fernandez, M., Brueck, W., Steinbach, K., Vorm, M.,... Merkler, D. (2013). Neuroprotective intervention by interferon-γ blockade prevents CD8+ T cell-mediated dendrite and synapse loss. Journal of Experimental Medicine, 210(10), 2087-2103. https://doi.org/10.1084/jem.20122143

MLA:

Kreutzfeldt, Mario, et al. "Neuroprotective intervention by interferon-γ blockade prevents CD8+ T cell-mediated dendrite and synapse loss." Journal of Experimental Medicine 210.10 (2013): 2087-2103.

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