CD4<sup>+</sup> T cells contribute to neurodegeneration in Lewy body dementia.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34648304.
- Also identified by DOI 10.1126/science.abf7266 and PMC identifier 9122025.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 <i>C-X-C motif chemokine receptor 4</i> (<i>CXCR4</i>) in CD4<sup>+</sup> 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 <i>interleukin 17A</i> expression by CD4<sup>+</sup> 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.
Medical subject headings
- Brain
- CD4-Positive T-Lymphocytes
- Lewy Body Disease
- Nerve Degeneration