Cardiac immunity and heart repair: Mechanism, challenge, and future direction

ABSTRACT: Immune signaling has emerged as a central regulator of cardiac biology, extending far beyond its traditionally recognized roles in pathology. From embryogenesis to adulthood, immune cells orchestrate key processes, including coronary vasculature formation, cardiomyocyte maturation, mitochondrial homeostasis, and extracellular matrix (ECM) remodeling. In the setting of myocardial injury, immune responses unfold in tightly choreographed phases, initially clearing necrotic debris and later facilitating scar formation and, in certain contexts, promoting tissue regeneration. Recent advances in single-cell and spatial transcriptomics have revealed the remarkable heterogeneity and plasticity of immune cell populations in the heart, highlighting their metabolic and phenotypic adaptability across developmental and disease contexts. Alongside these biological insights, therapeutic interest has grown in targeting specific immune pathways to modulate inflammation, enhance repair, and restore cardiac function. This review integrates discoveries from developmental immunology, cardiac injury models, and regenerative medicine to illustrate how the immune system underpins cardiac resilience and plasticity. By synthesizing molecular, cellular, and systems-level data, we present a cohesive view of cardioimmune interactions that opens new avenues for precision therapies aimed at heart repair and regeneration.