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Status |
Public on Sep 14, 2021 |
Title |
CD4+ T cells contribute to neurodegeneration in Lewy body dementia [CSF_and_PBMCs_Healthy and LBD] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Recent studies indicate that the adaptive immune system plays a role in Lewy body dementia (LBD). However, the mechanism regulating T cell brain homing in LBD is unknown. Here, we observed T cells adjacent to Lewy bodies and dopaminergic neurons in post-mortem LBD brains. Single-cell RNA sequencing of cerebrospinal fluid (CSF) identified upregulated expression of C-X-C Motif Chemokine Receptor 4 (CXCR4) in CD4+ T cells in LBD. CSF protein levels of the CXCR4 ligand, C-X-C Motif Chemokine Ligand 12 (CXCL12) were associated with neuroaxonal damage in LBD. Furthermore, we observed clonal expansion and upregulated Interleukin 17A expression by CD4+ T cells stimulated with a phosphorylated α-synuclein epitope. Thus, CXCR4-CXCL12 signaling may represent a mechanistic target for inhibiting pathological interleukin-17-producing T cell trafficking in LBD.
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Overall design |
scRNAseq of CSF cells from healthy (n=11) and LBD (n=11) subjects. Live cells were sorted with a live/dead SYTOX blue dye. Sequencing libraries were prepared using the 10X Genomics platform.
PBMCs from some of these subjects were also sequenced by scRNAseq.
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Contributor(s) |
Gate D, Leventhal O, Fehlmann T |
Citation(s) |
34648304 |
Submission date |
Dec 06, 2019 |
Last update date |
Dec 14, 2021 |
Contact name |
David Gate |
E-mail(s) |
dgate@northwestern.edu
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Phone |
8054044775
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Organization name |
Northwestern University
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Street address |
303 E Chicago Ave
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City |
Chicago |
State/province |
IL |
ZIP/Postal code |
60611 |
Country |
USA |
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Platforms (2) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
GPL28038 |
DNBSEQ-G400 (Homo sapiens) |
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Samples (35)
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Relations |
BioProject |
PRJNA593998 |
SRA |
SRP234979 |