| First Author | Terrabuio E | Year | 2025 |
| Journal | Nat Commun | Volume | 16 |
| Issue | 1 | Pages | 8372 |
| PubMed ID | 40993111 | Mgi Jnum | J:373113 |
| Mgi Id | MGI:8251386 | Doi | 10.1038/s41467-025-62405-6 |
| Citation | Terrabuio E, et al. (2025) CD103(-)CD8(+) T cells promote neurotoxic inflammation in Alzheimer's disease via granzyme K-PAR-1 signaling. Nat Commun 16(1):8372 |
| abstractText | Immune mechanisms contribute to the neuropathology of Alzheimer's disease (AD) but the role of adaptive immune cells is unclear. Here we show that the brain CD8(+) T cell compartment is dysregulated in AD patients and in the 3xTg-AD mouse model, accumulating activated CD103(-) tissue-resident memory T cells that produce large amounts of granzyme K (GrK). These CD103(-)CD8(+) T cells originate from the circulation and migrate into the brain using LFA-1 integrin. Ablation of brain CD103(-)CD8(+) T cells in 3xTg-AD mice ameliorates cognitive decline and reduces neuropathology. GrK induces neuronal dysfunction and tau hyperphosphorylation in human and mouse cells via protease-activated receptor-1 (PAR-1), which is expressed at higher levels in the AD brain, revealing a key immune-mediated neurotoxic axis. We conclude that communication between CD8(+) T cells and the nervous system is altered in AD, paving the way for therapies targeting T cell-dependent neurotoxic inflammation. |
