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Notch3+ Regulatory T cells Drive Autoimmune Neuroinflammation in Multiple Sclerosis

GSE253602 Mus musculus Expression profiling by high throughput sequencing 5 samples Submitted 2025/07/01 Platform GPL24247
Summary
The immune regulatory defects that promote neuroinflammation in multiple sclerosis (MS) remain unclear. We show that a specific regulatory T (Treg) cell subpopulation expressing Notch3 is increased in individuals with MS and in mice with experimental autoimmune encephalomyelitis (EAE). Notch3 is induced by the gut microbiota by toll-like receptor (TLR)-dependent mechanisms to promote EAE severity. Notch3 interacts with delta-like ligand 1 (DLL1) on microglia to subvert Treg cells into T helper 17 (Th17) cells. Notch3 Treg-specific deletion inhibits EAE by preventing Treg cell destabilization while simultaneously promoting the expansion of a novel tissue-resident neuropeptide receptor 1 (NPY1R)+ Treg cell population that suppressed pathogenic IFNg+ and GM-CSF+ T cells. Our studies thus identify altered Treg cell population dynamics as a fundamental pathogenic mechanism in autoimmune neuroinflammation.
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Also filed as BioProject PRJNA1066344 and SRA study SRP484533. Searching any of these in the dataset finder brings you back here.

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