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In a mouse disease model, Th17 lymphocytes induce microglial activation, blood\u2013brain barrier (BBB) dysfunction, and neural circuit impairment; however, the transcriptional programs underlying these effects, and the specific Th17-derived cytokines involved are unclear. Using mouse genetics, single-cell RNA sequencing, and spatial transcriptomics, we show that GAS infections induce inflammatory gene programs in microglia and brain endothelial cells (BECs), accompanied by downregulation of BBB-associated transcripts in BECs. Spatial transcriptomic analyses reveal that GAS-responsive microglia are enriched near infiltrating T cells. Several chemokines upregulated in microglia following GAS infection in mice are elevated in sera from affected patients. Conditional ablation of GM-CSF in CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells partially attenuates microglial chemokine gene expression, but does not restore BBB integrity. Neutralization of IL-17A partially rescues BBB transcriptional changes in BECs and reduces microglial chemokine expression; however, compensatory peripheral immune responses associated with persistent infection exacerbate BBB disruption. In contrast, microglia\/macrophage-specific deletion of IL-17 receptor A partially rescues BBB deficits following GAS infection. Together, these findings identify IL-17A\u2013IL-17RA signaling in microglia as a critical driver of BBB dysfunction after GAS infections.\n                <\/jats:p>","DOI":"10.64898\/2026.02.04.703836","type":"posted-content","created":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:25:13Z","timestamp":1770510313000},"source":"Crossref","is-referenced-by-count":0,"title":["Th17 effector cytokines induce shared and distinct microglial and endothelial cell responses in post-streptococcal encephalitis"],"prefix":"10.64898","author":[{"given":"Charlotte R.","family":"Wayne","sequence":"first","affiliation":[{"name":"Department of Neurology, Columbia University Irving Medical Center, New York, NY, 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U\u011fur","family":"Akcan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University Irving Medical Center, New York, NY, 10032, 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