Clonal CD8 T cells in the leptomeninges are locally controlled and influence microglia in human neurodegeneration
Hobson, R.; Levy, S. H. S.; Flaherty, D.; Xiao, H.; Ciener, B.; Reddy, H.; Singal, C.; Teich, A. F.; Shneider, N. A.; Bradshaw, E. M.; Elyaman, W.
Show abstract
Recent murine studies have highlighted a crucial role for the meninges in surveilling the central nervous system (CNS) and influencing CNS inflammation. However, how meningeal immunity is altered in human neurodegeneration and its potential effects on neuroinflammation is understudied. In the present study, we performed single-cell analysis of the transcriptomes and T cell receptor repertoire of 72,576 immune cells from 36 postmortem human brain and leptomeninges tissues from donors with neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimers disease, and Parkinsons disease. We identified the meninges as an important site of antigen presentation and CD8 T cell activation and clonal expansion and found that T cell activation in the meninges is a requirement for infiltration into the CNS. We further found that natural killer cells have the potential to negatively regulate T cell activation locally in the meninges through direct killing and are one of many regulatory mechanisms that work to control excessive neuroinflammation.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Meningeal inflammation in multiple sclerosis induces phenotypic changes in cortical microglia that differentially associate with neurodegeneration 95%
- Single-cell transcriptomic landscape of the neuroimmune compartment in amyotrophic lateral sclerosis brain and spinal cord 95%
- Defects in lysosomal function and lipid metabolism in human microglia harboring a TREM2 loss of function mutation 94%
Similar papers in this journal
- Temporally resolved single-cell RNA sequencing reveals protective and pathological responses during herpes simplex virus 1 CNS infection 94%
- High throughput identification of genetic regulators of microglial inflammatory processes in Alzheimer's disease 94%
- Molecular pathology of acute spinal cord injury in middle-aged mice 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.