Neurons under T Cell Attack Coordinate Phagocyte-Mediated Synaptic Stripping

Di Liberto, Giovanni and Pantelyushin, Stanislav and Kreutzfeldt, Mario and Page, Nicolas and Musardo, Stefano and Coras, Roland and Steinbach, Karin and Vincenti, Ilena and Klimek, Bogna and Lingner, Thomas and Salinas, Gabriela and Lin-Marq, Nathalie and Staszewski, Ori and Costa Jordão, Marta Joana and Wagner, Ingrid and Egervari, Kristof and Mack, Matthias and Bellone, Camilla and Blümcke, Ingmar and Prinz, Marco and Pinschewer, Daniel D. and Merkler, Doron. (2018) Neurons under T Cell Attack Coordinate Phagocyte-Mediated Synaptic Stripping. Cell, 175 (2). pp. 458-471.e19.

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Official URL: https://edoc.unibas.ch/76556/

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Experimental Virology (Pinschewer)
UniBasel Contributors:Pinschewer, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:12 May 2020 13:30
Deposited On:12 May 2020 13:30

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