The role of epigenetic regulation in cuproptosis, ferroptosis and NETosis in the pathogenesis of autoimmune diseases.

Ferroptosis, cuproptosis and NETosis are various important forms of non-apoptotic programmed cell death, with research involving these subtypes of cell death exponentially increased in recent years. Ferroptosis is a unique iron-dependent form of cell death that involves iron transport as well as redox homeostasis within the cell. Cuproposis is a new phenomenon of cell death, primarily driven by the excessive intracellular accumulation of copper ions, with its occurrence and development closely associated with mitochondrial dysfunction. NETosis on the other hand occurs due to the release of neutrophil extracellular traps by neutrophils upon their stimulation. Currently, various of types of autoimmune diseases (AD) have been clinically identified, with their etiology established to be multifactorial. In this review, we specifically investigate the correlation between these three non-apoptotic programmed cell deaths and the pathogenesis of AD, as well as elucidate the internal mechanisms involving miRNA, DNA methylation, histone modifications, related transcription factors, and non-coding RNAs from an epigenetic perspective. Additionally, we analyzed the molecular and pathophysiological mechanisms of ferroptosis, cupropopsis, and NETosis in the development of AD. By examining the therapeutic potential of emerging immune checkpoint targets, this review aims to offer novel insights and strategies to address the ongoing challenges in the prevention and treatment of autoimmune diseases.