系统性硬化症相关间质性肺病的纤维化机制新进展及靶向治疗策略
Recent Advances in the Fibrotic Mechanisms of Systemic Sclerosis-Associated Interstitial Lung Disease and Its Targeted Therapeutic Strategies
DOI: 10.12677/acm.2025.15123607, PDF,   
作者: 雷玉倩, 奚甘露, 张 利：延安大学医学院，陕西 延安；白智远*：延安大学附属医院老年呼吸科，陕西 延安
关键词: 纤维化；免疫发病机制；间质性肺病；系统性硬化症；靶向治疗；Fibrosis； Immunopathogenesis； Interstitial Lung Disease； Systemic Sclerosis； Targeted Therapy
摘要: 系统性硬化症相关间质性肺病(SSc-ILD)是系统性硬化症患者发病和死亡的主要原因，其特征是复杂的免疫病理机制和进行性纤维化。近期研究进展揭示了关键细胞参与者，包括T细胞、巨噬细胞、树突状细胞，以及TGF-β、PDGF、CTGF等促纤维化介质，并强调表观遗传重编程在维持成纤维细胞活化中的新兴作用。同时表观遗传重编程在维持成纤维细胞活化方面也发挥着重要作用。本综述总结了目前对免疫–纤维化相互作用的理解，并对现有疗法(例如吗替麦考酚酯、尼达尼布、托珠单抗和利妥昔单抗)和新型靶向疗法进行了批判性评估。特别关注新兴的免疫调节、抗纤维化和细胞疗法，包括CAR-T细胞疗法和间充质干细胞疗法，以及从肿瘤学领域重新开发的表观遗传调节剂的潜在应用。通过连接基础科学和临床实践，本综述概述了SSc-ILD不断变化的治疗格局，并重点介绍了未来研究和个性化干预的机会。
Abstract: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a leading cause of morbidity and mortality in patients with systemic sclerosis and is characterized by complex immunopathological mechanisms and progressive fibrosis. Recent research has identified key cellular participants, including T cells, macrophages, and dendritic cells, as well as profibrotic mediators such as TGF-β, PDGF, and CTGF. These studies also highlight the emerging role of epigenetic reprogramming in sustaining fibroblast activation. Epigenetic reprogramming has also been recognized as an important contributor to sustaining fibroblast activation. This review summarizes current understanding of immune-fibrotic interactions and provides a critical assessment of existing therapeutic approaches, such as mycophenolate mofetil, nintedanib, tocilizumab, and rituximab, along with emerging targeted therapies. Particular attention is given to novel immunomodulatory, antifibrotic, and cell-based interventions, including CAR-T cell therapy, mesenchymal stem cell therapy, and the potential application of epigenetic modulators repurposed from oncology. By bridging basic science with clinical practice, this review outlines the evolving therapeutic landscape of SSc-ILD and highlights opportunities for future research and personalized treatment strategies.
文章引用：雷玉倩, 奚甘露, 张利, 白智远. 系统性硬化症相关间质性肺病的纤维化机制新进展及靶向治疗策略[J]. 临床医学进展, 2025, 15(12): 1892-1904. https://doi.org/10.12677/acm.2025.15123607

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