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@ARTICLE{Frolov:278061,
author = {Frolov, Aleksej and Huang, Hao and Schütz, Dagmar and
Köhne, Maren Christin and Blank-Stein, Nelli and
Osei-Sarpong, Collins and Büttner, Maren and Elmzzahi,
Tarek and Khundadze, Mukhran and Zahid, Marina and Reuter,
Michael and Becker, Matthias and De Domenico, Elena and
Bonaguro, Lorenzo and Kallies, Axel and Morrison, Helen and
Hübner, Christian A and Händler, Kristian and Stumm, Ralf
and Mass, Elvira and Beyer, Marc D},
title = {{M}icroglia and {CD}8+ {T} cell activation precede neuronal
loss in a murine model of spastic paraplegia 15.},
journal = {Journal of experimental medicine},
volume = {222},
number = {7},
issn = {0022-1007},
address = {New York, NY},
publisher = {Rockefeller Univ. Press},
reportid = {DZNE-2025-00556},
pages = {e20232357},
year = {2025},
abstract = {In central nervous system (CNS) diseases characterized by
late-onset neurodegeneration, the interplay between innate
and adaptive immune responses remains poorly understood.
This knowledge gap is exacerbated by the prolonged
protracted disease course as it complicates the delineation
of brain-resident and infiltrating cells. Here, we conducted
comprehensive profiling of innate and adaptive immune cells
in a murine model of spastic paraplegia 15 (SPG15), a
complicated form of hereditary spastic paraplegia. Using
fate-mapping of bone marrow-derived cells, we identified
microgliosis accompanied by infiltration and local expansion
of T cells in the CNS of Spg15-/- mice. Single-cell analysis
revealed an expansion of disease-associated microglia (DAM)
and effector CD8+ T cells prior to neuronal loss. Analysis
of potential cell-cell communication pathways suggested
bidirectional interactions between DAM and effector CD8+ T
cells, potentially contributing to disease progression in
Spg15-/- mice. In summary, we identified a shift in
microglial phenotypes associated with the recruitment and
expansion of T cells as a new characteristic of Spg15-driven
neuropathology.},
keywords = {Animals / CD8-Positive T-Lymphocytes: immunology /
CD8-Positive T-Lymphocytes: pathology / Microglia:
immunology / Microglia: pathology / Disease Models, Animal /
Mice / Neurons: pathology / Neurons: immunology / Mice,
Knockout / Lymphocyte Activation: immunology / Spastic
Paraplegia, Hereditary: immunology / Spastic Paraplegia,
Hereditary: pathology / Mice, Inbred C57BL},
cin = {AG Beyer / AG Schultze / AG Bonaguro / AG Becker / PRECISE},
ddc = {610},
cid = {I:(DE-2719)1013035 / I:(DE-2719)1013038 /
I:(DE-2719)1016005 / I:(DE-2719)5000079 /
I:(DE-2719)1013031},
pnm = {351 - Brain Function (POF4-351) / 354 - Disease Prevention
and Healthy Aging (POF4-354) / 352 - Disease Mechanisms
(POF4-352)},
pid = {G:(DE-HGF)POF4-351 / G:(DE-HGF)POF4-354 /
G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40266307},
doi = {10.1084/jem.20232357},
url = {https://pub.dzne.de/record/278061},
}