Editorial: Crosstalk in ferroptosis, immunity & inflammation.

The rapid evolution of ferroptosis research has opened new therapeutic frontiers across various medical disciplines. Studies exploring anastasis—the recovery from ferroptotic stress—could unveil novel mechanisms of cellular resilience. Advanced bioinformatics analyses have identified key molecular signatures linking ferroptosis with immune infiltration, further reinforcing the importance of computational approaches in this field. Looking ahead, the development of reliable biomarkers, targeted inhibitors, and inducers of ferroptosis will be crucial. Moreover, integrating ferroptosis modulation with immunotherapy holds significant promise for clinical translation across a range of conditions, particularly in oncology and inflammatory diseases.

This Research Topic provides valuable insights into the crosstalk between ferroptosis, immunity, and inflammation across diverse disease models. By understanding its molecular mechanisms and interactions with immune responses, inflammation, and metabolic pathways, we can identify novel therapeutic targets and improve treatment strategies for a wide range of conditions. Future research should focus on ferroptosis-modulating strategies to enhance therapeutic efficacy, minimize disease progression, and improve patient outcomes. The findings presented in this Research Topic pave the way for future investigations and potential clinical applications, emphasizing the critical role of ferroptosis in immune regulation and disease pathogenesis.

Chronic metabolic disorders, including diabetes and obesity, are often accompanied by ferroptosis-driven tissue damage. Hyperglycemia-induced oxidative stress can lead to ferroptotic cell death in renal and vascular tissues, contributing to diabetic nephropathy and atherosclerosis. Understanding the metabolic regulation of ferroptosis could help in designing effective interventions for metabolic syndrome and related disorders ( 8 ). Additionally. Liu et al. have identified key ferroptosis-related genes involved in endometriosis pathogenesis, highlighting the potential for ferroptosis-targeting therapies to mitigate disease progression and immune dysfunction. Kidney diseases is a typical metabolic disorder. Dysregulation of iron homeostasis during ferroptotic processes significantly influences progression of kidney diseases, including acute kidney injury and renal fibrosis ( 9 , 10 ) ( Long et al. ). While alterations in lipid metabolism also modulate ferroptotic cell death. These findings highlight the need for further mechanistic studies to fully understand these pathways. In renal ischemia–reperfusion (I/R) injury, ferroptosis contributes to kidney damage, which is characterized by increased collagen deposition, α-SMA expression, and oxidative stress. Fer-1 treatment or ATF3 knockdown alleviated these changes while modulating Nrf2/HO-1 signaling. Additionally, exosomal miR-1306-5p release under hypoxia-reoxygenation promoted M2 macrophage polarization, linking ferroptosis to immune regulation in renal fibrosis ( Tang et al. ). Moreover, Li et al. ‘s study investigating the role of ferroptosis in acute kidney injury (AKI) revealed that GSTT1 and GSTM1 were significantly downregulated in the renal tubular cells of AKI patients and in cisplatin-treated mice. Notably, Gstm1/Gstt1 double knockout (DKO) mice, while phenotypically normal under baseline conditions, presented exacerbated kidney dysfunction, increased ROS levels, and severe ferroptosis following cisplatin administration, underscoring the contribution of GST enzymes to ferroptotic resistance in renal injury. In chronic obstructive pulmonary disease (COPD), ferroptosis-mediated alveolar epithelial cell death exacerbates disease progression. Exposure to electronic nicotine delivery systems (ENDS) has been linked to worsening COPD features, including emphysema, mucus accumulation, inflammation, and fibrosis, all of which are associated with lipid dysregulation and ferroptotic injury( Han et al. ). Beyond pulmonary diseases, ferroptosis also plays a crucial role in I/R injury, a pathological process affecting multiple organ systems, including the heart, brain, lung and kidneys. Ferroptotic cell death contributes to endothelial dysfunction, which in turn promotes vascular inflammation and atherosclerosis. In cardiovascular conditions such as heart failure and myocardial infarction, oxidative stress-induced ferroptosis of cardiomyocytes accelerates disease progression, particularly in cases involving iron overload. Additionally, ferroptosis has been implicated in cerebral I/R injury, where it exacerbates neuronal damage and neuroinflammation ( He et al. ), further linking ferroptotic mechanisms to both cardiovascular and neurological pathologies. Given its broad impact, targeting ferroptosis represents a promising therapeutic strategy for mitigating I/R injury, reducing vascular complications, and improving outcomes in cardiopulmonary diseases.