Immune cell dynamics and their role in cardiac injury: Mechanisms and therapeutic implications
Chunlei Liu, Rihan Wu, Hao Yang, Yong-ming Yao
Abstract
Cardiovascular injury initiates a temporally regulated immune cascade that governs both tissue damage and repair. Neutrophils, macrophages, dendritic cells, and T cells contribute distinct yet overlapping functions during acute inflammation, resolution, and chronic remodeling. This review synthesizes recent findings from single-cell transcriptomics, spatial omics, immunometabolism, and neuroendocrine–immune interactions to delineate immune cell dynamics across major cardiac diseases, including myocardial infarction, heart failure, viral myocarditis, hypertensive remodeling, and sepsis-induced cardiomyopathy. We further examine how immune cells communicate with cardiomyocytes, fibroblasts, endothelial cells, and neurohormonal regulators to shape the myocardial microenvironment. Particular emphasis is placed on macrophage polarization, regulatory T cell activity, extracellular vesicle–mediated signaling, and metabolic checkpoints as key determinants of immune behavior. Based on these mechanistic insights, we propose a framework for precision immunotherapy that integrates immune profiling, metabolic status, and neuroendocrine cues to guide individualized interventions. Emerging strategies—including low-dose interleukin-2, immune checkpoint blockade, mesenchymal stem cell–derived extracellular vesicles, and immunometabolic reprogramming—are highlighted as promising means to recalibrate immunity toward tissue repair. Overall, this review provides a translational perspective aimed at shifting cardiovascular therapy from non-specific immunosuppression to adaptive, stage-specific immunomodulation. • Immune cells dynamically regulate inflammation, repair, and remodeling after heart injury. • Different heart diseases trigger distinct immune responses with shared and unique features. • Heart cells, immune cells, and blood vessels interact via signals, contact, and ECM. • Preventing/treating heart damage requires precise immune modulation via targeted therapies.