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, Costa Jordão MJ, Wagner I, Egervari K, Mack M, Bellone C, Blümcke I, Prinz M, Pinschewer DD, Merkler D.
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. 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.
