伤口愈合
脊髓
髓样
趋化因子
CD8型
炎症
细胞毒性T细胞
T细胞
免疫学
生物
脊髓损伤
癌症研究
细胞生物学
神经科学
免疫系统
体外
生物化学
作者
Guiping Kong,Yayue Song,Yuyang Yan,Samantha Calderazzo,Madhu Sudhana Saddala,Fabian de Labastida Rivera,Jonathan D. Cherry,Noah Eckman,Eric A. Appel,Adam Velenosi,Vivek Swarup,Riki Kawaguchi,Susanna S. Ng,Brian Kwon,David Gate,Christian Engwerda,Luming Zhou,Simone Di Giovanni
出处
期刊:Neuron
[Elsevier]
日期:2025-01-13
卷期号:113 (5): 684-700.e8
被引量:5
标识
DOI:10.1016/j.neuron.2024.12.012
摘要
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-dependent 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 antibodies 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.
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