ArticleEMBO reports2023
Enhancing Spns2/S1P in macrophages alleviates hyperinflammation and prevents immunosuppression in sepsis.
Article in EMBO reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The core role of central nervous system in sepsis-related organ damage.Frontiers in immunology · 2025Pooled it
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Review
- Article
- Targeting SPHK1 by 8-HETrE attenuates MASH-Driven fibrosis via restoration of hepatic stellate cell mitochondrial dynamics.Cell biology and toxicology · 2026Article
- Macrophage metabolic reprogramming in sepsis-associated acute lung injury: mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- Type II Alveolar Epithelial Cells Promote Sepsis-Induced Immunosuppression in Alveolar Macrophages via Exosomal lncRNA Rmrp Release.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Immunometabolic Reprogramming in Experimental Sepsis: A Driver of Multiple Organ Dysfunction Syndrome.Journal of inflammation research · 2026Review
- Metabolic and post-translational modifications in sepsis-associated immune dysfunction: a conceptual framework.Frontiers in immunology · 2026Review
- Sphingolipid Metabolism in the Pathogenesis of Hashimoto's Thyroiditis.International journal of molecular sciences · 2025Review
- Chaihu Guizhi Ganjiang Decoction ameliorates chronic pancreatitis by modulating the SK1/S1P signaling pathway.Journal of natural medicines · 2025Article
- Sweet regulation - The emerging immunoregulatory roles of hexoses.Journal of advanced research · 2025Review
- Regulatory role of S1P and its receptors in sepsis-induced liver injury.Frontiers in immunology · 2025Review
- Pathogen-induced mitochondrial dysfunction: mechanistic insights, immune crosstalk, and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2025Review
- From "metabolic storm" to "immune paralysis": the dynamic evolution of macrophages and metabolism reprogramming in ARDS.Frontiers in immunology · 2025Review
- The role of m6A methylation genes in predicting poor prognosis in sepsis: identifying key biomarkers and therapeutic targets.European journal of medical research · 2024Article
- Spinster homolog 2/S1P signaling ameliorates macrophage inflammatory response to bacterial infections by balancing PGECell communication and signaling : CCS · 2024Article
- Baicalin attenuates PD-1/PD-L1 axis-induced immunosuppression in piglets challenged with Glaesserella parasuis by inhibiting the PI3K/Akt/mTOR and RAS/MEK/ERK signalling pathways.Veterinary research · 2024Article
- New insights into the role of mitochondrial metabolic dysregulation and immune infiltration in septic cardiomyopathy by integrated bioinformatics analysis and experimental validation.Cellular & molecular biology letters · 2024Article
- How do sphingosine-1-phosphate affect immune cells to resolve inflammation?Frontiers in immunology · 2024Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.