Transplantation Center, Lausanne University Hospital, Rue du Bugnon 44, CH-1010 Lausanne, Switzerland.
Division of Immunology and Allergy, Lausanne University Hospital, CH-1010 Lausanne, Switzerland.
Int J Mol Sci. 2024 Jun 3;25(11):6162. doi: 10.3390/ijms25116162.
Systemic lupus erythematosus (SLE) is an autoimmune disease affecting mostly women of child-bearing age. Immune dysfunction in SLE results from disrupted apoptosis which lead to an unregulated interferon (IFN) stimulation and the production of autoantibodies, leading to immune complex formation, complement activation, and organ damage. Lupus nephritis (LN) is a common and severe complication of SLE, impacting approximately 30% to 40% of SLE patients. Recent studies have demonstrated an alteration in mitochondrial homeostasis in SLE patients. Mitochondrial dysfunction contributes significantly to SLE pathogenesis by enhancing type 1 IFN production through various pathways involving neutrophils, platelets, and T cells. Defective mitophagy, the process of clearing damaged mitochondria, exacerbates this cycle, leading to increased immune dysregulation. In this review, we aim to detail the physiopathological link between mitochondrial dysfunction and disease activity in SLE. Additionally, we will explore the potential role of mitochondria as biomarkers and therapeutic targets in SLE, with a specific focus on LN. In LN, mitochondrial abnormalities are observed in renal cells, correlating with disease progression and renal fibrosis. Studies exploring cell-free mitochondrial DNA as a biomarker in SLE and LN have shown promising but preliminary results, necessitating further validation and standardization. Therapeutically targeting mitochondrial dysfunction in SLE, using drugs like metformin or mTOR inhibitors, shows potential in modulating immune responses and improving clinical outcomes. The interplay between mitochondria, immune dysregulation, and renal involvement in SLE and LN underscores the need for comprehensive research and innovative therapeutic strategies. Understanding mitochondrial dynamics and their impact on immune responses offers promising avenues for developing personalized treatments and non-invasive biomarkers, ultimately improving outcomes for LN patients.
系统性红斑狼疮（SLE）是一种自身免疫性疾病，主要影响育龄妇女。SLE 中的免疫功能障碍是由于凋亡失调引起的，导致干扰素（IFN）不受调节的刺激和自身抗体的产生，导致免疫复合物形成、补体激活和器官损伤。狼疮肾炎（LN）是 SLE 的常见且严重的并发症，影响约 30%至 40%的 SLE 患者。最近的研究表明，SLE 患者中线粒体动态平衡发生改变。线粒体功能障碍通过涉及中性粒细胞、血小板和 T 细胞的各种途径显著促进 1 型 IFN 的产生，从而对 SLE 的发病机制有重要贡献。有缺陷的线粒体自噬（清除受损线粒体的过程）加剧了这一循环，导致免疫失调增加。在这篇综述中，我们旨在详细阐述 SLE 中线粒体功能障碍与疾病活动之间的生理病理联系。此外，我们将探讨线粒体作为 SLE 标志物和治疗靶点的潜在作用，特别关注 LN。在 LN 中，观察到肾细胞中线粒体异常，与疾病进展和肾纤维化相关。探索细胞外线粒体 DNA 作为 SLE 和 LN 生物标志物的研究显示出有希望但初步的结果，需要进一步验证和标准化。在 SLE 中，使用二甲双胍或 mTOR 抑制剂等药物靶向线粒体功能障碍，在调节免疫反应和改善临床结局方面显示出潜力。SLE 和 LN 中线粒体、免疫失调和肾脏受累之间的相互作用强调了需要进行全面研究和创新治疗策略。了解线粒体动力学及其对免疫反应的影响为开发个性化治疗和非侵入性生物标志物提供了有希望的途径，最终改善 LN 患者的结局。
