程序性细胞死亡1在自身免疫性疾病中的作用：机制与治疗意义

摘要(中文译文)

自身免疫性疾病是由免疫系统与自身抗原相互作用引起的复杂疾病，涉及遗传、环境触发因素及其他细胞因素。程序性细胞死亡受体-1（PD-1）基因作为免疫调节中的关键因子，在类风湿关节炎、系统性红斑狼疮和强直性脊柱炎等自身免疫性疾病的研究中受到了广泛关注。尽管这些疾病的发病机制各不相同，但均表现为免疫耐受的破坏和免疫稳态的失衡。研究表明，在自身免疫性疾病的发展过程中，PD-1基因表达的变化、其与PD-L1和PD-L2的结合以及信号转导通路往往出现异常。这些异常可能导致T细胞和B细胞的过度活化，从而攻击自身组织。因此，靶向PD-1/PD-L1信号通路的治疗策略具有广阔的前景。增强PD-L1转录的基因治疗方法或小分子药物可以加强PD-1/PD-L1的结合并恢复抑制性信号，从而重新平衡免疫反应并改善患者的生活质量。此外，近期研究表明，靶向Vγ4γδT细胞以监测疾病进展和预后是另一种基于PD-1的潜在治疗策略。本综述聚焦于PD-1基因在自身免疫性疾病中的作用，系统阐述了PD-1及其配体的结构、分子功能和调控机制，同时深入分析了PD-1在自身免疫性疾病中的机制参与及其治疗前景。

Abstract

Autoimmune diseases are complex disorders caused by the interaction between the immune system and self-antigens, involving genetic, environmental triggers, and other cellular factors. The programmed cell death receptor-1 (PD-1) gene, as a critical factor in immune regulation, has garnered significant attention in the study of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis. Although the pathogenesis of these diseases varies, they all manifest as a breakdown in immune tolerance and an imbalance in immune homeostasis. Research has shown that in the development of autoimmune diseases, changes in PD-1 gene expression, its binding with PD-L1 and PD-L2, and signal transduction pathways are often abnormal. These abnormalities may lead to the overactivation of T cells and B cells, resulting in the attack on self-tissues. Consequently, therapeutic strategies targeting the PD-1/PD-L1 signaling pathway hold promising potential. Gene therapy approaches or small-molecule drugs that enhance PD-L1 transcription could strengthen PD-1/PD-L1 binding and restore inhibitory signaling, thereby rebalancing immune responses and improving patients' quality of life. Additionally, recent studies suggest that targeting Vγ4γδT cells to monitor disease progression and prognosis represents another potential PD-1-based therapeutic strategy. This review focuses on the role of the PD-1 gene in autoimmune diseases, systematically elaborating on the structure, molecular functions, and regulatory mechanisms of PD-1 and its ligands, while providing an in-depth analysis of PD-1's mechanistic involvement in autoimmune diseases and its therapeutic prospects.

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