Direksunthorn Thanyaporn, T Ahmed Abdulrahman, Pluetrattanabha Nakaraj, Uthirapathy Subasini, Ballal Suhas, Singh Abhayveer, Al-Hetty Hussein Riyadh Abdul Kareem, Devi Anita, Sharma Girish Chandra, Yumashev Alexey
School of Medicine, Walailak University, Nakhon Si Thammarat, Thailand.
College of Nursing, University of Al Maarif, Al Anbar, 31001, Iraq.
J Physiol Biochem. 2025 Apr 16. doi: 10.1007/s13105-025-01078-7.
Since its introduction in 2012, ferroptosis has garnered significant attention from researchers over the past decade. Unlike autophagy and apoptosis, ferroptosis is an atypical iron-dependent programmed cell death that falls under necrosis. It is regulated by various cellular metabolic and signaling processes, which encompass amino acid, lipid, iron, and mitochondrial metabolism. The initiation of ferroptosis occurs through iron-dependent phospholipid peroxidation. Notably, ferroptosis exhibits a dual effect and is associated with various diseases. A significant challenge lies in managing autoimmune disorders with unknown origins that stem from the reactivation of the immune system. Two contributing factors to autoimmunity are the aberrant stimulation of cell death and the inadequate clearance of dead cells, which can expose or release intracellular components that activate the immune response. Ferroptosis is distinct from other forms of cell death, such as apoptosis, necroptosis, autophagy, and pyroptosis, due to its unique morphological, biochemical, and genetic characteristics and specific relationship with cellular iron levels. Recent studies indicate that immune cells can both induce and undergo ferroptosis. To better understand how ferroptosis influences immune responses and its imbalance in disease, a molecular understanding of the relationship between ferroptosis and immunity is essential. Consequently, further research is needed to develop immunotherapeutics that target ferroptosis. This review primarily focuses on the role of ferroptosis in immune-related disorders.
自2012年被提出以来，铁死亡在过去十年中受到了研究人员的广泛关注。与自噬和凋亡不同，铁死亡是一种非典型的、依赖铁的程序性细胞死亡，属于坏死范畴。它受多种细胞代谢和信号传导过程调控，包括氨基酸、脂质、铁和线粒体代谢。铁死亡的启动通过铁依赖的磷脂过氧化作用发生。值得注意的是，铁死亡具有双重作用，且与多种疾病相关。一个重大挑战在于应对起源不明的自身免疫性疾病，这些疾病源于免疫系统的重新激活。自身免疫的两个促成因素是细胞死亡的异常刺激和死亡细胞清除不足，这可能会暴露或释放激活免疫反应的细胞内成分。由于其独特的形态、生化和遗传特征以及与细胞铁水平的特定关系，铁死亡不同于其他形式的细胞死亡，如凋亡、坏死性凋亡、自噬和焦亡。最近的研究表明，免疫细胞既能诱导铁死亡，也能发生铁死亡。为了更好地理解铁死亡如何影响免疫反应及其在疾病中的失衡，从分子层面理解铁死亡与免疫之间的关系至关重要。因此，需要进一步研究以开发针对铁死亡的免疫疗法。本综述主要关注铁死亡在免疫相关疾病中的作用。
