CXCL13型
细胞生物学
CD8型
再生(生物学)
主要组织相容性复合体
趋化因子
坐骨神经
生物
T细胞
神经科学
免疫系统
免疫学
解剖
趋化因子受体
作者
Luming Zhou,Guiping Kong,Ilaria Palmisano,Maria Teresa Cencioni,Matt C. Danzi,Francesco De Virgiliis,Jessica Chadwick,Greg Crawford,Zicheng Yu,Fred de Winter,John L. Bixby,Radhika Puttagunta,Joost Verhaagen,C Pospori,Cristina Lo Celso,Jessica Strid,Marina Botto,Simone Di Giovanni
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2022-05-13
卷期号:376 (6594)
被引量:29
标识
DOI:10.1126/science.abd5926
摘要
Aging is associated with increased prevalence of axonal injuries characterized by poor regeneration and disability. However, the underlying mechanisms remain unclear. In our experiments, RNA sequencing of sciatic dorsal root ganglia (DRG) revealed significant aging-dependent enrichment in T cell signaling both before and after sciatic nerve injury (SNI) in mice. Lymphotoxin activated the transcription factor NF-κB, which induced expression of the chemokine CXCL13 by neurons. This in turn recruited CXCR5+CD8+ T cells to injured DRG neurons overexpressing major histocompatibility complex class I. CD8+ T cells repressed the axonal regeneration of DRG neurons via caspase 3 activation. CXCL13 neutralization prevented CXCR5+CD8+ T cell recruitment to the DRG and reversed aging-dependent regenerative decline, thereby promoting neurological recovery after SNI. Thus, axonal regeneration can be facilitated by antagonizing cross-talk between immune cells and neurons.
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