Shengnan Wang , Mengting Li , Han Shen , Wenjing Zhou , Jiuyuan Sun , Qingsong Tang , Hongman Liu , Wencheng Zhang , Zhenya Shen , Weiqian Chen
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引用次数: 0
Abstract
Myocardial infarction (MI) remains a formidable global health challenge, as current therapies are hindered by excessive inflammation that exacerbates cardiac dysfunction and accelerates disease progression. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) and CD28 are T-lymphocyte receptors with opposing roles in T-cell activation: CD28 binding to CD80/CD86 ligands on dendritic cells (DCs) mediates co-stimulation, whereas CTLA-4 engagement delivers inhibitory signals. In our present study, mannosylated cytotoxic T-lymphocyte antigen 4 (CTLA-4)-presenting small extracellular vesicles (CM@sEVs) were engineered for targeted MI therapy. By disrupting the CD80/86-CD28 costimulatory signaling, these CM@sEVs counteract dendritic cell (DC)-driven CD8+ T cell priming, thereby mitigating ischemic immunopathology while supporting myocardial repair. Notably, distinct from existing T-cell modulatory therapies, our CM@sEVs uniquely reshape in vivo T-cell dynamics directly through DC-dependent mechanisms, offering a precise and stable strategy for ischemic cardiomyopathy.
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