Small Extracellular Vesicles Derived from Altered Peptide Ligand‐Loaded Dendritic Cell Act as A Therapeutic Vaccine for Spinal Cord Injury Through Eliciting CD4+ T cell‐Mediated Neuroprotective Immunity

• Published in: Advanced science 2024-01, Vol.11 (3), p.e2304648-n/a
• Main Authors: Wang, Sikai, Li, Guanglei, Liang, Xiongjie, Wu, Zexuan, Chen, Chao, Zhang, Fawang, Niu, Jiawen, Li, Xuefeng, Yan, Jinglong, Wang, Nanxiang, Li, Jing, Wang, Yufu
• Format: Article
• Language: English
• Subjects: Animals; Antigens; antigen‐specific immune; Cytokines; Dendritic Cells; Extracellular vesicles; Extracellular Vesicles - metabolism; Flow cytometry; Ligands; Lymphocytes; Mice; neuroprotective immunity; Peptides; Rats; Rats, Sprague-Dawley; small extracellular vesicles; Spinal cord injuries; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - therapy; spinal cord injury; T-Lymphocytes, Regulatory; Vaccines; Vaccines - pharmacology; Vaccines - therapeutic use
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202304648

The balance among different CD4+ T cell subsets is crucial for repairing the injured spinal cord. Dendritic cell (DC)‐derived small extracellular vesicles (DsEVs) effectively activate T‐cell immunity. Altered peptide ligands (APLs), derived from myelin basic protein (MBP), have been shown to affect CD4+ T cell subsets and reduce neuroinflammation levels. However, the application of APLs is challenging because of their poor stability and associated side effects. Herein, it is demonstrate that DsEVs can act as carriers for APL MBP87‐99A91 (A91‐DsEVs) to induce the activation of 2 helper T (Th2) and regulatory T (Treg) cells for spinal cord injury (SCI) in mice. These stimulated CD4+ T cells can efficiently “home” to the lesion area and establish a beneficial microenvironment through inducing the activation of M2 macrophages/microglia, inhibiting the expression of inflammatory cytokines, and increasing the release of neurotrophic factors. The microenvironment mediated by A91‐DsEVs may enhance axon regrowth, protect neurons, and promote remyelination, which may support the recovery of motor function in the SCI model mice. In conclusion, using A91‐DsEVs as a therapeutic vaccine may help induce neuroprotective immunity in the treatment of SCI. This study uses Dendritic cell‐derived small extracellular vesicles (DsEVs) loaded with APL MBP87‐99A91 (A91‐DsEVs). A91‐DsEVs promotes activation of Th2 and Treg cells, which can home to the injured spinal cord and induce neuroprotective immunity. The treatment with A91‐DsEVs can enhance axon regrowth, neuronal survival, and remyelination, which may support the functional motor recovery in the SCI model mice.