Clonally expanded, targetable, natural killer-like NKG7 T cells seed the aged spinal cord to disrupt myeloid-dependent wound healing
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Spinal cord injury (SCI) increasingly affects aged individuals, where functional impairment and mortality are
highest. However, the aging-dependent mechanisms underpinning tissue damage remain elusive. Here, we
find that natural killer-like T (NKLT) cells seed the intact aged human and murine spinal cord and multiply
further after injury. NKLT cells accumulate in the spinal cord via C-X-C motif chemokine receptor 6 and ligand
16 signaling to clonally expand by engaging with major histocompatibility complex (MHC)-I-expressing
myeloid cells. NKLT cells expressing natural killer cell granule protein 7 (Nkg7) disrupt myeloid-cell-depen dent wound healing in the aged injured cord. Nkg7 deletion in mice curbs NKLT cell degranulation to
normalize the myeloid cell phenotype, thus promoting tissue repair and axonal integrity. Monoclonal anti bodies neutralizing CD8+ T cells after SCI enhance neurological recovery by promoting wound healing.
Our results unveil a reversible role for NKG7+
CD8+ NKLT cells in exacerbating tissue damage, suggesting
a clinically relevant treatment for SCI.
highest. However, the aging-dependent mechanisms underpinning tissue damage remain elusive. Here, we
find that natural killer-like T (NKLT) cells seed the intact aged human and murine spinal cord and multiply
further after injury. NKLT cells accumulate in the spinal cord via C-X-C motif chemokine receptor 6 and ligand
16 signaling to clonally expand by engaging with major histocompatibility complex (MHC)-I-expressing
myeloid cells. NKLT cells expressing natural killer cell granule protein 7 (Nkg7) disrupt myeloid-cell-depen dent wound healing in the aged injured cord. Nkg7 deletion in mice curbs NKLT cell degranulation to
normalize the myeloid cell phenotype, thus promoting tissue repair and axonal integrity. Monoclonal anti bodies neutralizing CD8+ T cells after SCI enhance neurological recovery by promoting wound healing.
Our results unveil a reversible role for NKG7+
CD8+ NKLT cells in exacerbating tissue damage, suggesting
a clinically relevant treatment for SCI.
Date Issued
2025-03-05
Date Acceptance
2024-12-12
Citation
Neuron, 2025, 113 (5), pp.684-700.e8
ISSN
0896-6273
Publisher
Elsevier BV
Start Page
684
End Page
700.e8
Journal / Book Title
Neuron
Volume
113
Issue
5
Copyright Statement
© 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39809279
PII: S0896-6273(24)00911-5
Subjects
CD8(+) T cells
NKG7
NKLT cells
aging
granzyme K
regeneration
repair
spinal cord injury
wound healing
Animals
Spinal Cord Injuries
Mice
Myeloid Cells
Humans
Wound Healing
Killer Cells, Natural
Aging
Spinal Cord
CD8-Positive T-Lymphocytes
Female
Mice, Inbred C57BL
Male
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2025-01-13