Nucleic Acid Vaccine Targeting Nogo-66 Receptor and Paired Immunoglobulin-Like Receptor B as an Immunotherapy Strategy for Spinal Cord Injury in Rats
Nucleic Acid Vaccine Targeting Nogo-66 Receptor and Paired Immunoglobulin-Like Receptor B as an Immunotherapy Strategy for Spinal Cord Injury in Rats
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靶向 Nogo-66 受体和配对免疫球蛋白样受体 B 的核酸疫苗作为大鼠脊髓损伤的免疫治疗策略
DOI：
10.1007/s13311-019-00718-3
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发表时间：
2019-04-01
影响因子：
5.7
通讯作者：
Wang, Yong-Tang
中科院分区：
文献类型：
--
作者：
Lu, Xiu-Min;Mao, Min;Wang, Yong-Tang
Nogo-66受体（NgR）和成对免疫球蛋白样受体B（Pir B）是髓鞘相关抑制剂（迈斯）的两种常见受体，因此在MAIs诱导的脊髓损伤（SCI）后再生的抑制性信号传导中起重要作用。基于保护性自身免疫的概念，疫苗方法可以诱导针对髓磷脂中抑制剂的抗体的产生，例如使用纯化的髓磷脂、脊髓匀浆或迈斯受体NgR，以阻断抑制作用并促进SCI模型中的功能恢复。然而，由于MAIs介导的抑制性信号传导中涉及的分子和机制的复杂性，这些免疫治疗策略产生了不一致的结果。因此，我们推测，选择和修饰自身抗原，并共同调节多个靶点，可能会更有效地修复损伤的脊髓，促进功能恢复。本研究选择NgR和PirB构建双靶向的粒细胞-巨噬细胞集落刺激因子-NgR-PirB（GMCSF-NgR-PirB）核酸疫苗，并观察其在大鼠脊髓损伤模型中的免疫治疗效果。结果表明，这种疫苗接种可以刺激NgR和PirB抗体的产生，阻断各种迈斯介导的抑制作用，促进脊髓损伤后的神经再生和功能恢复。这些发现表明，针对NgR和PirB的核酸疫苗接种可能是SCI和其他中枢神经系统疾病和损伤的有希望的治疗策略。
Nogo-66 receptor (NgR) and paired immunoglobulin-like receptor B (PirB) are two common receptors of various myelin-associated inhibitors (MAIs) and, thus, play an important role in MAIs-induced inhibitory signalling of regeneration following spinal cord injury (SCI). Based on the concept of protective autoimmunity, vaccine approaches could induce the production of antibodies against inhibitors in myelin, such as using purified myelin, spinal cord homogenates, or MAIs receptor NgR, in order to block the inhibitory effects and promote functional recovery in SCI models. However, due to the complication of the molecules and the mechanisms involved in MAIs-mediated inhibitory signalling, these immunotherapy strategies have yielded inconsistent outcomes. Therefore, we hypothesized that the choice and modification of self-antigens, and co-regulating multiple targets, may be more effective in repairing the injured spinal cord and improving functional recovery. In this study, NgR and PirB were selected to construct a double-targeted granulocyte-macrophage colony stimulating factor-NgR-PirB (GMCSF-NgR-PirB) nucleic acid vaccine, and investigate the efficacy of this immunotherapy in a spinal cord injury model in rats. The results showed that this vaccination could stimulate the production of antibodies against NgR and PirB, block the inhibitory effects mediated by various MAIs, and promote nerve regeneration and functional recovery after spinal cord injury. These findings suggest that nucleic acid vaccination against NgR and PirB can be a promising therapeutic strategy for SCI and other central nervous system diseases and injuries.