Loading…

CD4 + T cells contribute to neurodegeneration in Lewy body dementia

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 o...

Full description

Saved in:
Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2021-11, Vol.374 (6569), p.868-874
Main Authors: Gate, David, Tapp, Emma, Leventhal, Olivia, Shahid, Marian, Nonninger, Tim J, Yang, Andrew C, Strempfl, Katharina, Unger, Michael S, Fehlmann, Tobias, Oh, Hamilton, Channappa, Divya, Henderson, Victor W, Keller, Andreas, Aigner, Ludwig, Galasko, Douglas R, Davis, Mark M, Poston, Kathleen L, Wyss-Coray, Tony
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
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 postmortem LBD brains. Single-cell RNA sequencing of cerebrospinal fluid (CSF) identified up-regulated expression of ( ) 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 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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.abf7266