The Role of Oxidative Stress in Modulating Inflammatory Cell Death

Oxidative stress and redox imbalance are increasingly recognized as fundamental regulators of inflammatory cell death. Beyond their classical reputation for causing cellular damage, reactive oxygen species (ROS) serve as context-dependent signaling molecules that govern the initiation, amplification, and resolution of regulated necrotic pathways such as pyroptosis, ferroptosis, necroptosis, PANoptosis, and other forms of lytic or immunogenic cell death. Critically, ROS also act as a converging signal at the crosstalk between these distinct cell death modalities, engaging shared molecular components, such as RIPK1/RIPK3, caspases, and inflammasome sensors, to influence how a cell commits to, switches between, or integrates pyroptotic, necroptotic, ferroptotic, and PANoptotic programs. These processes have far-reaching consequences across infection, sterile inflammation, cancer, neurodegeneration, cardiovascular disorders, metabolic syndrome, and aging. Yet, despite major advances, our understanding of how oxidative signaling intersects with organelle dysfunction, inflammasome activation, lipid peroxidation, and immune regulation remains incomplete. Bridging these gaps is essential to decipher how redox biology shapes inflammation, tissue integrity, and disease outcomes.This Research Topic aims to unify mechanistic, translational, and systems-level studies that dissect how oxidative stress modulates inflammatory forms of cell death and, reciprocally, how these cell death programs influence redox homeostasis and inflammatory signaling. We encourage contributions elucidating the molecular interplay between ROS generation, antioxidant defenses, metabolic rewiring, and cell fate decisions. Studies defining the role of mitochondrial ROS, NADPH oxidases, iron-dependent oxidative injury, lipid peroxidation, and redox-sensitive signaling nodes are especially welcome. Submissions that link redox signaling to innate immunity, inflammasome dynamics, tissue-specific inflammation, and disease pathogenesis will be particularly valuable. Work exploring redox-based biomarkers, emerging imaging modalities, and therapeutic interventions that manipulate these pathways is also invited.By focusing on the highly interlinked domains of redox biology, inflammation, and regulated cell death, this collection aims to provide a timely and authoritative resource for the field. This Topic will appeal to investigators working in immunology, redox and mitochondrial biology, metabolism, toxicology, infection, cancer, neuroinflammation, and translational medicine. We welcome Original Research, Reviews, Mini Reviews, Methods, and Perspectives that define unifying mechanisms, uncover novel molecular circuits, and identify therapeutic opportunities at the convergence of oxidative stress and inflammatory cell death.Themes of interest include, but are not limited to:• ROS and redox signaling in the regulation of pyroptosis, ferroptosis, necroptosis, PANoptosis, and related inflammatory pathways• ROS as a molecular hub coordinating crosstalk and switching between distinct inflammatory cell death pathways• Oxidative stress and inflammasome activation, including NLRP3 and other innate immune sensors• Mitochondrial dysfunction and redox regulation of organelle stress in inflammatory cell death• Lipid peroxidation, iron metabolism, and antioxidant systems in ferroptosis and inflammatory tissue injury• Metabolic and immune crosstalk shaping oxidative and inflammatory cell death outcomes• NADPH oxidases, thiol-based redox systems, and redox-sensitive regulators of cytotoxicity• Oxidative stress-driven inflammatory cell death in infection, sepsis, autoimmunity, cancer, and neurodegeneration• Roles of oxidative stress in barrier tissues, immune cells, stroma, and organ-specific inflammation• Connections between cell death, DAMP release, cytokine signaling, and tissue remodeling• Therapeutic modulation of oxidative stress or inflammatory cell death pathways• Multi-omics, imaging, and single-cell approaches to characterize redox-dependent death programs• Comparative and integrative studies distinguishing protective versus pathogenic oxidative stress responses Topic editors: Ratnakar Reddy Bynigeri, Ankit Pandeya, Praveen Yerramothu Source: https://www.frontiersin.org/research-topics/83363/the-role-of-oxidative-stress-in-modulating-inflammatory-cell-death