NATURAL killer (NK) cells were found to drive cardiac damage and worsen outcomes following myocardial infarction, according to new research exploring immune mechanisms in heart injury.
Myocardial infarction remains a leading cause of heart failure worldwide, with long-term outcomes shaped not only by the initial ischemic event but also by the body’s immune response. While inflammation is known to contribute to adverse cardiac remodelling, the role of cytotoxic immune cells such as NK cells has remained poorly understood.
NK Cells and Cardiac Damage
In this study, researchers showed that NK cell activity increased rapidly after acute cardiac injury. In mouse models, NK cells were recruited to the injured myocardium through CCR2-dependent pathways and became activated within the ischemic tissue.
Once activated, NK cells released granzyme B, a cytotoxic molecule that directly triggered cardiomyocyte apoptosis. This process amplified tissue damage, contributing to adverse ventricular remodelling and impaired cardiac function.
Importantly, NK cell responses were shown to be causative rather than incidental. Genetic deletion or pharmacological depletion of NK cells reduced cardiomyocyte death, limited inflammation, and improved cardiac function. Conversely, enhancing NK cell activity using an anti-NKG2A monoclonal antibody worsened myocardial injury and accelerated progression towards heart failure.
Role of NK Cells Extends Beyond the Heart
Beyond their local effects in the heart, NK cells were also found to influence systemic immune processes. The researchers demonstrated that NK cells regulate bone marrow myelopoiesis through the production of granulocyte-macrophage colony-stimulating factor, linking cardiac injury to broader immune activation.
Analysis of human ischemic heart tissue further supported these findings, revealing a distinct NK cell and transcriptomic signature in the early stages of myocardial infarction. This suggests that the mechanisms observed in preclinical models may be relevant to human disease.
However, the study was largely conducted in animal models, which may limit direct clinical translation. Further research is needed to determine whether targeting NK cells can be safely and effectively applied in patients.
Overall, the findings position NK cells as a promising therapeutic target. Modulating this immune response could help reduce cardiac damage, limit adverse remodelling, and improve recovery following myocardial infarction.
Reference
Cohen R et al. NK cells promote cardiac cell death and regulate myelopoiesis in myocardial infarction. Nat Commun. 2026;DOI:10.1038/s41467-026-71334-x.
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