Type-I IFNs in EAE drive synaptic transcriptional responses in neurons and astrocytes in the brain
- 1Duke University School of Medicine
Abstract
Neuronal pathology plays a prominent role in the cognitive and neuropathic symptoms of multiple sclerosis; however, little is known about these pathological signals to neurons in the brain and their consequences on cognition. 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. In summary, this study elucidates multiple steps of the pathogenesis of EAE pathology within the brain independent of the spinal cord.
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BibTeX
@misc{oneil2026typei,
title = {{Type-I IFNs in EAE drive synaptic transcriptional responses in neurons and astrocytes in the brain}},
author = {S. M. O'Neil and H. Min and L. Xu and A. J. Filiano},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.23.753833},
url = {https://www.biorxiv.org/content/10.64898/2026.09.23.753833v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Type-I IFNs in EAE drive synaptic transcriptional responses in neurons and astrocytes in the brain
AU - S. M. O'Neil
AU - H. Min
AU - L. Xu
AU - A. J. Filiano
PY - 2026
DA - 2026/09/23
PB - bioRxiv
DO - 10.64898/2026.09.23.753833
UR - https://www.biorxiv.org/content/10.64898/2026.09.23.753833v1
AB - Neuronal pathology plays a prominent role in the cognitive and neuropathic symptoms of multiple sclerosis; however, little is known about these pathological signals to neurons in the brain and their consequences on cognition. 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. In summary, this study elucidates multiple steps of the pathogenesis of EAE pathology within the brain independent of the spinal cord.
ER -