Type-I IFNs in EAE drive synaptic transcriptional responses in neurons and astrocytes in the brain

Here, using a transgenic reporter of IFN signaling with spatial RNA-sequencing, we determined myelin-specific autoimmune T cells enter the brain parenchyma through the interface between the fimbria and third ventricle.

Here, astrocytes and microglia express high levels of MHC-II-associated transcripts. Using this reporter, we also showed microglia within the brain are not direct responders of IFNs, but express transcripts associated with synaptic pruning, potentially contributing to pathological remodeling of neuronal circuits. Moreover, both type-I and type-II IFNs are required for T cells to infiltrate the brain and initiate an IFN response associated with synaptic and metabolic programs in neurons and astrocytes in the cortex and hippocampus.