Neurons under T Cell Attack Coordinate Phagocyte-Mediated Synaptic Stripping

Journal article


Publication Details

Author(s): Di Liberto G, Pantelyushin S, Kreutzfeldt M, Page N, Musardo S, Coras R, Steinbach K, Vincenti I, Klimek B, Lingner T, Salinas G, Lin-Marq N, Staszewski O, Jordao MJC, Wagner I, Egervari K, Mack M, Bellone C, Blümcke I, Prinz M, Pinschewer DD, Merkler D
Journal: Cell
Publication year: 2018
Volume: 175
Journal issue: 2
Pages range: 458-471.e19
ISSN: 0092-8674


Abstract

Inflammatory disorders of the CNS are frequently accompanied by synaptic loss, which is thought to involve phagocytic microglia and complement components. However, the mechanisms accounting for aberrant synaptic connectivity in the context of CD8+ T cell-driven neuronal damage are poorly understood. Here, we profiled the neuronal translatome in a murine model of encephalitis caused by CD8+ T cells targeting antigenic neurons. Neuronal STAT1 signaling and downstream CCL2 expression were essential for apposition of phagocytes, ensuing synaptic loss and neurological disease. Analogous observations were made in the brains of Rasmussen's encephalitis patients. In this devastating CD8+ T cell-driven autoimmune disease, neuronal STAT1 phosphorylation and CCL2 expression co-clustered with infiltrating CD8+ T cells as well as phagocytes. Taken together, our findings uncover an active role of neurons in coordinating phagocyte-mediated synaptic loss and highlight neuronal STAT1 and CCL2 as critical steps in this process that are amenable to pharmacological interventions.


FAU Authors / FAU Editors

Blümcke, Ingmar Prof. Dr.
Lehrstuhl für Neuropathologie


External institutions with authors

Albert-Ludwigs-Universität Freiburg
Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG)
Universität Basel
Universitätsklinikum Göttingen
Universitätsklinikum Regensburg
University of Geneva / Université de Genève (UNIGE)


How to cite

APA:
Di Liberto, G., Pantelyushin, S., Kreutzfeldt, M., Page, N., Musardo, S., Coras, R.,... Merkler, D. (2018). Neurons under T Cell Attack Coordinate Phagocyte-Mediated Synaptic Stripping. Cell, 175(2), 458-471.e19. https://dx.doi.org/10.1016/j.cell.2018.07.049

MLA:
Di Liberto, Giovanni, et al. "Neurons under T Cell Attack Coordinate Phagocyte-Mediated Synaptic Stripping." Cell 175.2 (2018): 458-471.e19.

BibTeX: 

Last updated on 2019-22-03 at 08:23