Shock (Augusta, Ga.) · 2025
Mechanisms of Sepsis From a Metabolic Immunology Perspective: A Bidirectional Mendelian Randomization and Single-Cell Sequencing Study of CD39 + Cells.
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Xue Jinfang, Zhou Ning, Li Quan, Wang Ruijie, Li Yan, Zhu Huadong, Lv Chuanzhu
Аннотация
BACKGROUND: Interactions between immune phenotypes and metabolites in sepsis pathogenesis remain poorly defined. We integrated Mendelian randomization (MR) and single-cell transcriptomics to investigate metabolic mediation in immune-sepsis associations.
METHODS: Bidirectional two-sample MR analyzed sepsis genome-wide association studies (11,643 cases), 1,400 metabolites, and 731 immune phenotypes. Single-cell analysis of GSE167363 (sepsis vs. controls) included clustering, differential expression and pathway enrichment.
RESULTS: CD39 expression was upregulated in sepsis immune cells. MR-identified CD3 + CD39 + CD8 + T cells as risk factors for sepsis incidence (odds ratio = 1.053, P = 0.008) and 28-day mortality (odds ratio = 1.108, P = 0.037). These cells correlated with 73 metabolites, notably androsterone sulfate, which mediated 4.97% of sepsis risk ( P = 0.026).
CONCLUSION: CD39 + CD8 + T cells drive sepsis progression through metabolic intermediates like androsterone sulfate, highlighting immunometabolic crosstalk as a therapeutic target.
METHODS: Bidirectional two-sample MR analyzed sepsis genome-wide association studies (11,643 cases), 1,400 metabolites, and 731 immune phenotypes. Single-cell analysis of GSE167363 (sepsis vs. controls) included clustering, differential expression and pathway enrichment.
RESULTS: CD39 expression was upregulated in sepsis immune cells. MR-identified CD3 + CD39 + CD8 + T cells as risk factors for sepsis incidence (odds ratio = 1.053, P = 0.008) and 28-day mortality (odds ratio = 1.108, P = 0.037). These cells correlated with 73 metabolites, notably androsterone sulfate, which mediated 4.97% of sepsis risk ( P = 0.026).
CONCLUSION: CD39 + CD8 + T cells drive sepsis progression through metabolic intermediates like androsterone sulfate, highlighting immunometabolic crosstalk as a therapeutic target.