Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.670646
Keywords
PD-L1; spinal cord injury; neuropathic pain; macrophages/microglial; polarization; ERK1/2; p38
Categories
Funding
- National Natural Science Foundation of China [81871828, 81802218, 81702141]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [JX10213715]
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PD-L1 is significantly upregulated after SCI and highly expressed on macrophages/microglia at the injury epicenter. Deletion of PD-L1 results in worse locomotor recovery and more serious pathological pain, which is associated with increased polarization of M1-like macrophages/microglia. Mechanistic analysis suggests that PD-L1 may improve functional outcomes following SCI by inhibiting phosphorylation of p38 and ERK1/2.
Background: Traumatic spinal cord injury (SCI) causes severe motor dysfunction and persistent central neuropathic pain (Nep), which has not yet been effectively cured. Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and contributes to the immune-suppressive in tumor microenvironment. However, the role of PD-L1 in regulating inflammatory response and Nep after SCI remains unclear. A growing amount of researches have begun to investigate the effect of PD-L1 on macrophages and microglia in recent years. Considering the pivotal role of macrophages/microglia in the inflammatory response after SCI, we proposed the hypothesis that PD-L1 improved the recovery of locomotor and sensory functions after SCI through regulating macrophages and microglia. Methods: The mice SCI model was established to determine the changes in expression patterns of PD-L1. Meanwhile, we constructed PD-L1 knockout mice to observe differences in functional recovery and phenotypes of macrophages/microglia post-SCI. Results: In present study, PD-L1 was significantly upregulated after SCI and highly expressed on macrophages/microglia at the injury epicenter. PD-L1 knockout (KO) mice showed worse locomotor recovery and more serious pathological pain compared with wild-type (WT) mice. Furthermore, deletion of PD-L1 significantly increased the polarization of M1-like macrophages/microglia. Mechanistic analysis revealed that PD-L1 may improve functional outcomes following SCI by inhibiting phosphorylation of p38 and ERK1/2. Conclusions: Our observations implicate the involvement of PD-L1 in recovery of SCI and provide a new treatment strategy for the prevention and treatment of this traumatic condition.
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