Neurons under T Cell Attack Coordinate Phagocyte-Mediated Synaptic Stripping
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 (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 175
Pages Range: 458-471.e19
Journal Issue: 2
DOI: 10.1016/j.cell.2018.07.049
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.
Authors with CRIS profile
Involved external institutions
Albert-Ludwigs-Universität Freiburg
Germany (DE)
University of Geneva / Université de Genève (UNIGE)
Switzerland (CH)
Universitätsklinikum Göttingen
Germany (DE)
Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG)
Switzerland (CH)
Universität Basel
Switzerland (CH)
Universitätsklinikum Regensburg
Germany (DE)
Germany (DE)
University of Geneva / Université de Genève (UNIGE)
Switzerland (CH)
Universitätsklinikum Göttingen
Germany (DE)
Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG)
Switzerland (CH)
Universität Basel
Switzerland (CH)
Universitätsklinikum Regensburg
Germany (DE)
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.
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