{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:18:38Z","timestamp":1792790318591,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,25]]},"group-title":"Neuroscience","reference-count":34,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Neurological Disorders and Stroke","award":["R01NS123084"],"award-info":[{"award-number":["R01NS123084"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>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.<\/jats:p>\n                <jats:p>IFNs activate astrocytes and neurons in EAE brain<\/jats:p>\n                <jats:sec>\n                  <jats:title>Summary<\/jats:title>\n                  <jats:p>Autoreactive T cells in EAE activate IFN-responsive pathways in neurons and astrocytes in the brain. T cells enter the brain through the fimbria and drive transcriptional signatures of synaptic dysfunction in neurons and synaptic pruning in microglia.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.23.753833","type":"posted-content","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:05:10Z","timestamp":1790409910000},"source":"Crossref","is-referenced-by-count":0,"title":["Type-I IFNs in EAE drive synaptic transcriptional responses in neurons and astrocytes in the brain"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6045-2012","authenticated-orcid":false,"given":"Shane M.","family":"O\u2019Neil","sequence":"first","affiliation":[{"name":"Marcus Center for Cellular Cures, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5823-6780","authenticated-orcid":false,"given":"Hyunjung","family":"Min","sequence":"additional","affiliation":[{"name":"Marcus Center for Cellular Cures, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9171-6510","authenticated-orcid":false,"given":"Li","family":"Xu","sequence":"additional","affiliation":[{"name":"Marcus Center for Cellular Cures, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4329-0151","authenticated-orcid":false,"given":"Anthony J.","family":"Filiano","sequence":"additional","affiliation":[{"name":"Marcus Center for Cellular Cures, Duke University School of Medicine, Durham, NC, USA"},{"name":"Department of Neurosurgery, Duke University School of Medicine, Durham, NC, USA."},{"name":"Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC, USA"},{"name":"Department of Pathology, Duke University School of Medicine, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092918450794000_2026.09.23.753833v1.1","doi-asserted-by":"crossref","first-page":"3858","DOI":"10.1038\/s41467-026-72383-y","article-title":"A comparative transcriptomic analysis of mouse demyelination models and multiple sclerosis lesions","volume":"17","year":"2026","journal-title":"Nature Communications"},{"key":"2026092918450794000_2026.09.23.753833v1.2","doi-asserted-by":"crossref","first-page":"5016","DOI":"10.4049\/jimmunol.161.9.5016","article-title":"Transgenic Expression of IFN-\u03b1 in the Central Nervous System of Mice Protects Against Lethal Neurotropic Viral Infection but Induces Inflammation and Neurodegeneration","volume":"161","year":"1998","journal-title":"The Journal of Immunology"},{"key":"2026092918450794000_2026.09.23.753833v1.3","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24224"},{"key":"2026092918450794000_2026.09.23.753833v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01806-0"},{"key":"2026092918450794000_2026.09.23.753833v1.5","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5804-08.2009"},{"key":"2026092918450794000_2026.09.23.753833v1.6","doi-asserted-by":"crossref","unstructured":"Florescu, A. , M. 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