LAG3延缓小胶质细胞炎性衰老促进脊髓损伤修复的机制研究
LAG3 Delays Microglial Inflammatory Senescence to Promote Spinal Cord Injury Repair
马云龙 1高翔 1盛蕾 1严兵 1周晓中1
作者信息
- 1. 苏州大学附属第二医院骨科，苏州 215004
- 折叠
摘要
背景与目的：脊髓损伤（SCI）后继发炎症是加剧组织损伤的重要因素，细胞衰老参与其中但机制不明。免疫检查点淋巴细胞激活基因3（LAG3）可能调控小胶质细胞衰老及炎症。本研究探索SCI后细胞衰老特征及LAG3在小胶质细胞衰老和炎症中的作用。方法：采用小鼠脊髓钳夹模型，通过SA-β-Gal染色与免疫荧光鉴定衰老细胞类型；利用单细胞测序数据分析筛选Lag3；体外构建Lag3敲低/过表达BV2细胞，LPS诱导炎性衰老模型，检测炎症和衰老变化。结果：SCI后衰老细胞主要是小胶质细胞，其炎症调节能力下降，Lag3表达下调。Lag3主要见于稳态小胶质细胞，SCI后7天达表达峰值。体外过表达Lag3抑制基础及LPS诱导的炎症，减轻炎性衰老；敲低Lag3则加重炎症与衰老。结论：SCI引起小胶质细胞衰老和炎症调节能力下降；Lag3在稳态小胶质细胞表达，损伤后急性期上调；Lag3可抑制小胶质细胞炎症反应，延缓炎性衰老。
Abstract
Background and Objective: Secondary inflammation following spinal cord injury (SCI) is a critical factor exacerbating tissue damage. Cellular senescence is implicated in this process, but the underlying mechanisms remain unclear. The immune checkpoint molecule lymphocyte activation gene 3 (LAG3) may regulate microglial senescence and inflammation. This study aims to characterize cellular senescence after SCI and investigate the role of LAG3 in microglial senescence and inflammation.
Methods: A mouse spinal cord clamp injury model was established. Senescent cell types were identified using SA-β-Gal staining and immunofluorescence. Single-cell RNA sequencing data were analyzed to screen for Lag3. Lag3 knockdown or overexpression was performed in BV2 cells in vitro, followed by LPS-induced inflammatory senescence modeling to assess changes in inflammation and senescence.
Results: Microglia were identified as the predominant senescent cell type after SCI, exhibiting reduced immunomodulatory capacity and downregulated Lag3 expression. LAG3 was mainly expressed in homeostatic microglia, peaking at 7 days post-injury. In vitro, LAG3 overexpression suppressed both basal and LPS-induced inflammation and alleviated inflammatory senescence, whereas LAG3 knockdown exacerbated inflammation and senescence.
Conclusion: SCI induces microglial senescence and impairs their immunomodulatory capacity. LAG3 is expressed in homeostatic microglia and is upregulated during the acute phase after injury. LAG3 inhibits microglial inflammatory responses and delays inflammatory senescence.关键词
脊髓损伤/小胶质细胞/细胞衰老/LAG3/神经炎症Key words
Spinal cord injury/Microglia/Cellular senescence/LAG3/Neuroinflammation引用本文复制引用
马云龙,高翔,盛蕾,严兵,周晓中.LAG3延缓小胶质细胞炎性衰老促进脊髓损伤修复的机制研究[EB/OL].(2026-06-16)[2026-06-18].http://www.paper.edu.cn/releasepaper/content/202606-46.学科分类
基础医学/神经病学、精神病学/生物科学研究方法、生物科学研究技术/细胞生物学
