Cell death signaling and immune regulation: new perspectives on targeted therapy for sepsis

Cell death is essential for the preservation of tissue homeostasis, regulating inflammatory responses, and shaping immune status. The mechanism of cell death includes apoptosis, pyroptosis, necroptosis, ferroptosis and autophagy. The onset, progression, and unfavorable prognosis of sepsis are closely associated with these pathways. Here, the mechanisms associated with these five major cell death pathways in sepsis are reviewed, emphasizing two core aspects of the condition: excessive inflammation and immune suppression. These pathways play a fundamental role in modulating these characteristics and offer novel therapeutic prospects. The study provides valuable insights and detailed analyses, making a significant contribution to ongoing research in this domain. The interconnected nature of cell death is highlighted, not only by examining the distinct roles of individual pathways but also by exploring the interactions between different pathways and the crosstalk among key signaling molecules or pathways, including the caspase family, gasdermin family, and NF-κB pathway. Further research should continue to investigate well-established cell death mechanisms while also identifying previously unknown pathways. Therapeutic strategies targeting cell death pathways hold broad application potential. However, during the transition from preclinical research to clinical application, several challenges remain, including limitations of experimental models, as well as the safety and efficacy of treatments. Additionally, the development of personalized treatment approaches tailored to the unique immune profiles of patients is crucial for advancing precision medicine. In conclusion, the present review offers an extensive analysis of the diverse roles of cell death in sepsis, with novel insights into disease mechanisms and guiding therapeutic developments.