标题： 椎间盘退变的免疫机制与免疫调节策略 显示英文标题

标题： Immunological mechanisms and immunoregulatory strategies in intervertebral disc degeneration

摘要： 椎间盘无血管且维持免疫特权。然而，在椎间盘退变（IDD）过程中，这一屏障被破坏，导致广泛的免疫细胞浸润和局部炎症。在退变的椎间盘中，巨噬细胞、T淋巴细胞、中性粒细胞以及颗粒髓源性抑制细胞（G-MDSCs）是关键参与者，表现出功能异质性。包括核因子κB（NF-κB）、白细胞介素-17（IL-17）以及核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎性小体激活在内的炎性通路失调激活，驱动局部促炎反应，导致细胞凋亡和细胞外基质（ECM）降解。基于外泌体的治疗、CRISPR/Cas9介导的基因编辑以及载有趋化因子的水凝胶系统等创新性免疫疗法，在重塑椎间盘的免疫微环境方面显示出潜力。这些策略能够调节失调的免疫反应，并为组织再生创造支持性环境。然而，目前的研究尚未完全阐明炎性记忆和免疫代谢轴的机制，同时在平衡组织再生与免疫稳态方面面临挑战。未来研究应采用单细胞和空间转录组学等跨学科方法，绘制IDD的全面免疫图谱，阐明细胞间互作和信号网络，并开发结合靶向免疫调节与再生工程的综合疗法，从而促进有效IDD治疗方法的临床转化。 显示英文摘要

摘要： Intervertebral discs are avascular and maintain immune privilege. However, during intervertebral disc degeneration (IDD), this barrier is disrupted, leading to extensive immune cell infiltration and localized inflammation. In degenerated discs, macrophages, T lymphocytes, neutrophils, and granulocytic myeloid-derived suppressor cells (G-MDSCs) are key players, exhibiting functional heterogeneity. Dysregulated activation of inflammatory pathways, including nuclear factor kappa-B (NF-kappaB), interleukin-17 (IL-17), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, drives local pro-inflammatory responses, leading to cell apoptosis and extracellular matrix (ECM) degradation. Innovative immunotherapies, including exosome-based treatments, CRISPR/Cas9-mediated gene editing, and chemokine-loaded hydrogel systems, have shown promise in reshaping the immunological niche of intervertebral discs. These strategies can modulate dysregulated immune responses and create a supportive environment for tissue regeneration. However, current studies have not fully elucidated the mechanisms of inflammatory memory and the immunometabolic axis, and they face challenges in balancing tissue regeneration with immune homeostasis. Future studies should employ interdisciplinary approaches such as single-cell and spatial transcriptomics to map a comprehensive immune atlas of IDD, elucidate intercellular crosstalk and signaling networks, and develop integrated therapies combining targeted immunomodulation with regenerative engineering, thereby facilitating the clinical translation of effective IDD treatments.