Th17 Effector Cytokines Induce Shared and Distinct Microglial and Endothelial Cell Responses in a Mouse Model for Post-Streptococcal Encephalitis

Authors

• Charlotte Wayne
• Uğur Akcan
• Travis Faust
• Violeta Durán-Laforet
• Danny Jamoul
• Luca Bremner
• Nicole Ampatey
• Büşra Akcan
• Sarah Ho
• Bogoljub Ciric, Thomas Jefferson UniversityFollow
• Shannon Delaney
• Wendy Vargas
• Susan Swedo
• Vilas Menon
• Dorothy Schafer
• Tyler Cutforth
• Dritan Agalliu

Document Type

Article

Publication Date

8-11-2026

Comments

This article is the author’s final published version in Nature Communications, Volume 17, Issue 1, 2026, Article number 9658.

The published version is available at https://doi.org/10.1038/s41467-026-76232-w. Copyright © The Author(s) 2026.

Abstract

Group A Streptococcus (GAS) infections cause neuropsychiatric complications in children, but the mechanisms linking peripheral infection to brain dysfunction remain unclear. Using mouse genetics, single-cell RNA sequencing, and spatial transcriptomics, we show that GAS infections induce inflammatory transcriptional programs in microglia and brain endothelial cells (BECs), accompanied by loss of blood-brain barrier (BBB) gene expression in female mice. Spatial transcriptomic analyses reveal that GAS-responsive microglia localize near infiltrating CD4+ T cells. Several microglial chemokines induced in mice are elevated in sera from affected patients. Deletion of GM-CSF in CD4⁺ T cells partially reduces microglial chemokine gene expression, without restoring BBB integrity. In contrast, IL-17A neutralization partially rescues BBB transcriptional changes, but not BBB dysfunction, and reduces microglial chemokine expression. Microglia-specific deletion of IL-17 receptor A partially restores BBB integrity after GAS infections. Our findings identify microglial IL-17A-IL17RA signaling as a potential mediator of BBB dysfunction and neuroinflammation after GAS infections.

Recommended Citation

Wayne, Charlotte; Akcan, Uğur; Faust, Travis; Durán-Laforet, Violeta; Jamoul, Danny; Bremner, Luca; Ampatey, Nicole; Akcan, Büşra; Ho, Sarah; Ciric, Bogoljub; Delaney, Shannon; Vargas, Wendy; Swedo, Susan; Menon, Vilas; Schafer, Dorothy; Cutforth, Tyler; and Agalliu, Dritan, "Th17 Effector Cytokines Induce Shared and Distinct Microglial and Endothelial Cell Responses in a Mouse Model for Post-Streptococcal Encephalitis" (2026). Department of Neurology Faculty Papers. Paper 412.
https://jdc.jefferson.edu/neurologyfp/412

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

42717209

Language

English