Systemic lupus erythematosus (SLE) and its renal manifestation Lupus nephritis (LN) are characterized by a dysregulated immune system, autoantibodies, and injury to the renal parenchyma. Iron accumulation and ferroptosis in the immune effectors and renal tubules are recently identified pathological features in SLE and LN. Ferroptosis is an iron dependent non-apoptotic form of regulated cell death and ferroptosis inhibitors have improved disease outcomes in murine models of SLE, identifying it as a novel druggable target. In this review, we discuss novel mechanisms by which iron accumulation and ferroptosis perpetuate immune cell mediated pathology in SLE/LN. We highlight intra-renal dysregulation of iron metabolism and ferroptosis as an underlying pathogenic mechanism of renal tubular injury. The basic concepts of iron biology and ferroptosis are also discussed to expose the links between iron, cell metabolism and ferroptosis, that identify intracellular pro-ferroptotic enzymes and their protein conjugates as potential targets to improve SLE/LN outcomes.

中文翻译：

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系统性红斑狼疮和狼疮性肾炎中铁稳态和铁死亡的功能后果

系统性红斑狼疮 (SLE) 及其肾脏表现 狼疮性肾炎 (LN) 的特点是免疫系统失调、自身抗体和肾实质损伤。最近发现免疫效应器和肾小管中的铁积累和铁死亡是 SLE 和 LN 的病理特征。铁死亡是一种铁依赖性非凋亡形式的受调节细胞死亡，铁死亡抑制剂改善了 SLE 小鼠模型的疾病结果，将其确定为一种新的药物靶标。在这篇综述中，我们讨论了 SLE/LN 中铁积累和铁死亡使免疫细胞介导的病理学持续存在的新机制。我们强调肾内铁代谢失调和铁死亡是肾小管损伤的潜在致病机制。还讨论了铁生物学和铁死亡的基本概念，以揭示铁、细胞代谢和铁死亡之间的联系，将细胞内促铁死亡酶及其蛋白质缀合物确定为改善 SLE/LN 结局的潜在靶标。