Enhancing Spns2/S1P in macrophages alleviates hyperinflammation and prevents immunosuppression in sepsis

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-infl

SUBMITTER: Dr. Chao Fang 

PROVIDER: S-SCDT-10_15252-EMBR_202256635 | biostudies-other |

REPOSITORIES: biostudies-other