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- W4382011072 abstract "Abstract Sepsis is a leading cause of in‐hospital mortality resulting from a dysregulated response to infection. Novel immunomodulatory therapies targeting macrophage metabolism have emerged as an important focus for current sepsis research. However, understanding the mechanisms underlying macrophage metabolic reprogramming and how they impact immune response requires further investigation. Here, we identify macrophage‐expressed Spinster homolog 2 (Spns2), a major transporter of sphingosine‐1‐phosphate (S1P), as a crucial metabolic mediator that regulates inflammation through the lactate‐reactive oxygen species (ROS) axis. Spns2 deficiency in macrophages significantly enhances glycolysis, thereby increasing intracellular lactate production. As a key effector, intracellular lactate promotes pro‐inflammatory response by increasing ROS generation. The overactivity of the lactate‐ROS axis drives lethal hyperinflammation during the early phase of sepsis. Furthermore, diminished Spns2/S1P signaling impairs the ability of macrophages to sustain an antibacterial response, leading to significant innate immunosuppression in the late stage of infection. Notably, reinforcing Spns2/S1P signaling contributes to balancing the immune response during sepsis, preventing both early hyperinflammation and later immunosuppression, making it a promising therapeutic target for sepsis." @default.
- W4382011072 created "2023-06-27" @default.
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- W4382011072 date "2023-06-26" @default.
- W4382011072 modified "2023-10-17" @default.
- W4382011072 title "Enhancing Spns2/S1P in macrophages alleviates hyperinflammation and prevents immunosuppression in sepsis" @default.
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- W4382011072 doi "https://doi.org/10.15252/embr.202256635" @default.
- W4382011072 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37358015" @default.
- W4382011072 hasPublicationYear "2023" @default.
- W4382011072 type Work @default.