biostudies-literatureZhuang JShaanxi Youth Rising Stars in Science and TechnologyKey Research and Development Program of Shaanxi ProvinceShaanxi Province Key Industry Innovation Chain ProjectNational Natural Science Foundation of ChinaInnovation Capability Support Program of ShaanxiShenzhen Science and Technology Program0663https://www.ebi.ac.uk/biostudies/studies/S-EPMC11959697biostudies-literatureUnknown8Sepsis, a life-threatening inflammatory disorder characterized by multiorgan failure, arises from a dysregulated immune response to infection. Modulating macrophage polarization has emerged as a promising strategy to control sepsis-associated inflammation. The endogenous metabolite itaconate has shown anti-inflammatory potential by suppressing the stimulator of interferon genes (STING) pathway, but its efficacy is inhibited by hyperactive glycolysis, which sustains macrophage overactivation. Here, we revealed a critical crosstalk between the itaconate-STING axis and glycolysis in macrophage-mediated inflammation. Building on this interplay, we developed a novel nanoparticle LDO (lonidamine disulfide 4-octyl-itaconate), a self-assembled metabolic regulator integrating an itaconate derivativResearch (Washington, D.C.)A Self-Assembled Metabolic Regulator Reprograms Macrophages to Combat Cytokine Storm and Boost Sepsis Immunotherapy.PMC119596972023-ZDLSF-592022SF-374JCYJ20240813150807010821736822021KJXX-922024ZC-KJXX-119Yang LLu XSun BHai YFan RZhao MHan BLuo LWang WWei GZhang CZhang BZhuang JfalseA Self-Assembled Metabolic Regulator Reprograms Macrophages to Combat Cytokine Storm and Boost Sepsis Immunotherapy.Sepsis, a life-threatening inflammatory disorder characterized by multiorgan failure, arises from a dysregulated immune response to infection. Modulating macrophage polarization has emerged as a promising strategy to control sepsis-associated inflammation. The endogenous metabolite itaconate has shown anti-inflammatory potential by suppressing the stimulator of interferon genes (STING) pathway, but its efficacy is inhibited by hyperactive glycolysis, which sustains macrophage overactivation. Here, we revealed a critical crosstalk between the itaconate-STING axis and glycolysis in macrophage-mediated inflammation. Building on this interplay, we developed a novel nanoparticle LDO (lonidamine disulfide 4-octyl-itaconate), a self-assembled metabolic regulator integrating an itaconate derivativ2025-01-01T00:00:00Z20252026-04-08T19:47:18.284Z2026-04-08T14:29:05.649ZS-EPMC119596974017101610.34133/research.0663