研究人员发现，坐骨神经背根神经节（DRG）的RNA测序显示，在小鼠坐骨神经损伤（SNI）之前和之后，T细胞信号传导都有明显的衰老依赖性富集。淋巴毒素激活了转录因子NF-κB，诱导了神经元对趋化因子CXCL13的表达。这反过来又将CXCR5+CD8+T细胞招募到过度表达主要组织相容性复合体I的受伤DRG神经元。CXCL13中和阻止了CXCR5+CD8+T细胞对DRG的招募，并逆转了衰老依赖性的再生能力下降，从而促进了SNI后的神经系统恢复。因此，通过拮抗免疫细胞和神经元之间的交叉对话，可以促进轴突的再生。
据悉，衰老与轴索损伤的发生率增加有关，其特点是再生能力差和残疾。然而，其基本机制仍不清楚。
附：英文原文
Title: Reversible CD8 T cell–neuron cross-talk causes aging-dependent neuronal regenerative decline
Author: Luming Zhou, Guiping Kong, Ilaria Palmisano, Maria Teresa Cencioni, Matt Danzi, Francesco De Virgiliis, Jessica S. Chadwick, Greg Crawford, Zicheng Yu, Fred De Winter, Vance Lemmon, John Bixby, Radhika Puttagunta, Joost Verhaagen, Constandina Pospori, Cristina Lo Celso, Jessica Strid, Marina Botto, Simone Di Giovanni
Issue&Volume: 2022-05-13
Abstract: 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.
DOI: abd5926
Source: https://www.science.org/doi/10.1126/science.abd5926