@article{69aaea706ebc4a75b531bb8e77788e72,
title = "CD4+ T cells contribute to neurodegeneration in Lewy body dementia",
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 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 a-synuclein epitope. Thus, CXCR4-CXCL12 signaling may represent a mechanistic target for inhibiting pathological interleukin-17-producing T cell trafficking in LBD.",
author = "David Gate and Emma Tapp and Olivia Leventhal and Marian Shahid and Nonninger, {Tim J.} and Yang, {Andrew C.} and Katharina Strempfl and Unger, {Michael S.} and Tobias Fehlmann and Hamilton Oh and Divya Channappa and Henderson, {Victor W.} and Andreas Keller and Ludwig Aigner and Galasko, {Douglas R.} and Davis, {Mark M.} and Poston, {Kathleen L.} and Tony Wyss-Coray",
note = "Funding Information: This work was supported by a National Institute of Neurologic Disease and Stroke K99/R00 Pathway to Independence Award (NS112458-01A1) (D.G.); an Irene Diamond Fund/AFAR Postdoctoral Transition Award in Aging (D.G.); a National Institutes of Health National Institute on Aging (NIA) F32 Fellowship (AG055255-01A1) (D.G.); the FFG Momentia Project 867741 (L.A.); Austrian Science Fund (FWF) Project P 31362- B34 (L.A.); FFG Project 867741 PMU FFF E-20/32/169-UNG (L.A.); the Howard Hughes Medical Institute (M.M.D.); NIH U19 AG065156, R01 NS115114, P30 AG066515, and P50 NS062684 (K.L.P.); Michael J. Fox Foundation for Parkinson's Research Grants 020756, 16921, and 18411 (K.L.P.); the Lewy Body Dementia Association (K.L.P.); Alzheimer's Drug Discovery Foundation (K.L.P.); Sanofi US Services, Inc. (K.L.P.); the Cure Alzheimer's Fund (T.W.-C.); the NOMIS Foundation (T.W.-C.); NIA R01 AG045034 05 (T.W.-C.); and the NIA-funded Stanford Alzheimer's Disease Research Center P50AG047366 (V.W.H.). Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works",
year = "2021",
month = nov,
day = "12",
doi = "10.1126/science.abf7266",
language = "English (US)",
volume = "374",
pages = "868--874",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6569",
}