Programmed cell death ligand-1 exerts neuroprotective effects in a mouse model of spinal cord injury by modulating T cell immunity
- VernacularTitle:程序性细胞死亡配体-1通过调节T细胞免疫在脊髓损伤小鼠模型中发挥神经保护作用
- Author:
Wenxu DONG
1
;
Shouyu GUO
2
;
Bo HU
1
Author Information
- Publication Type:Journal Article
- Keywords: spinal cord injury (SCI); programmed cell death ligand-1 (PD-L1); T cell; inflammation; PI3K/Akt-mTOR signaling pathway
- From: Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(6):927-933
- CountryChina
- Language:Chinese
- Abstract: [Objective] The aim of this study was to investigate the protective role of programmed cell death ligand-1 (PD-L1) in a mouse model of spinal cord injury (SCI) by regulating T cell immunity and the PI3K/Akt/mTOR signaling pathway. [Methods] C57BL/6 mice used to establish SCI models were divided into the sham operation group (Sham), SCI group, SCI+ PD-L1 antibody group (SCI+ Ab), and SCI+ PD-L1 protein group (SCI+ PRO). c57BL/6 mice and PD-L1 knockout mice were used for SCI mapping, and they were divided into the sham operation group (Sham WT), PD-L1 knockout sham operation group (Sham PD-L1 KO), SCI model group (SCI WT), and PD-L1 knockout SCI model group (SCI PD-L1 KO). Western blotting and qRT-PCR were applied to detect the expression of PD-L1 in spinal cord tissues at different time points after SCI; mouse motor function was assessed by the Basso Mouse Motor Scale (BMS); changes in the levels of inflammatory factors and T-cell subpopulations after SCI were analyzed using qRT-PCR and flow cytometry; and Western blotting was used to detect changes in the PI3K/Akt/mTOR signaling pathway activation. [Results] PD-L1 expression was upregulated in spinal cord tissues of mice subjected to SCI palliation, peaking on day 7. Compared with the SCI PD-L1 KO group, mice in the SCI WT group had significantly higher BMS scores at 7, 14, and 28 days after SCI (P<0.05), and the levels of inflammatory factors IL-1α, IL-2, IFN-γ and TNF-α were significantly lower on day 7 after palpation (P<0.05). Compared with the SCI+ PBS group, mice in the SCI+ PRO group had significantly higher Foxp3 levels and significantly lower Th1 and Th17 levels. Foxp3 levels were significantly higher, but Th1 and Th17 cell levels were significantly lower, and Th2 and Treg cell levels were significantly higher (P<0.05). The phosphorylation of the PI3K/Akt/mTOR signaling pathway was significantly higher in the SCI WT group mice than the SCI PD-L1 KO group ones (P<0.05). In contrast, the phosphorylation of PI3K/Akt/mTOR signaling pathway was significantly lower in the SCI+ PRO group than in the SCI+ PBS group and the SCI+ Ab group (P<0.05). [Conclusion] PD-L1 plays a neuroprotective role by regulating the balance of Th1, Th17, Th2 and Treg cells and inhibiting the PI3K/Akt/mTOR signaling pathway, thereby reducing the inflammatory response after SCI. PD-L1 is expected to be a new target for the treatment of SCI.
