CD4 + T cells contribute to neurodegeneration in Lewy body dementia
Gate D, Tapp E, Leventhal O, Shahid M, Nonninger TJ, Yang AC, Strempfl K, Unger MS et al.. Science (New York, N.Y.), 2021-10-14
Topic: Inflammation, microglia and astrocytes
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 postmortem LBD brains. Single-cell RNA sequencing of cerebrospinal fluid (CSF) identified up-regulated 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 up-regulated 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.
Key findings
- Recent studies indicate that the adaptive immune system plays a role in Lewy body dementia (LBD).
- Here, we observed T cells adjacent to Lewy bodies and dopaminergic neurons in postmortem LBD brains.
- 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 up-regulated interleukin 17A expression by CD4 + T cells stimulated with a phosphorylated α-synuclein epitope.
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Study details
- Evidence strengthLow
How this study scored 48/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Science (New York, N.Y.)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34648304) |
| Free to read | 2 / 2 | Free to read |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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APA 7th
Gate, D., Tapp, E., Leventhal, O., Shahid, M., Nonninger, T. J., Yang, A. C., et al. (2021). CD4 + T cells contribute to neurodegeneration in Lewy body dementia. Science (New York, N.Y.). https://doi.org/10.1126/science.abf7266
Vancouver
Gate D, Tapp E, Leventhal O, Shahid M, Nonninger TJ, Yang AC, et al. CD4 + T cells contribute to neurodegeneration in Lewy body dementia. Science (New York, N.Y.). 2021. doi:10.1126/science.abf7266. PMID: 34648304.
BibTeX
@article{gate2021-34648304,
author = {Gate, D. and Tapp, E. and Leventhal, O. and Shahid, M. and Nonninger, T. J. and Yang, A. C. and Strempfl, K. and Unger, M. S. and others},
title = {{CD4 + T cells contribute to neurodegeneration in Lewy body dementia}},
journal = {Science (New York, N.Y.)},
year = {2021},
doi = {10.1126/science.abf7266},
pmid = {34648304},
url = {https://doi.org/10.1126/science.abf7266}
}
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