NK cells promote cardiac cell death and regulate myelopoiesis in myocardial infarction

作者：Raphael M. Cohen, Vincent Duval, Rida Al-Rifai, Sidrah Maryam, Icia Santos-Zas, Rayan Braik, Marc Diedisheim, Charlène Jouve, Simon Nicoletti, Sara Thietart, Théo Guyon, Luna Chetrit, Maria Kral, Yvonne Döring, C Weber, Alexandre Loupy, Orianne Domengé, Marine Livrozet, Jean‐Sébastien Hulot, Ecem T. Sakalli, Giuseppe Rizzo, Antoine-Emmanuel Saliba, Marie Piollet, P. Bruneval, Alain Tedgui, Soraya Taleb, Olivier Hermine, Ian P. Wicks, Jean-Sebastien Silvestre, Sikander Hayat, Clément Cochain, Éric Vivier, Hafid Ait-Oufella · 发表于：Nature Communications · 年份：2026 · DOI：10.1038/s41467-026-71334-x · 被引用次数：1 · 研究领域：Cardiac Fibrosis and Remodeling、Immune Cell Function and Interaction、Atherosclerosis and Cardiovascular Diseases

Ischemic heart failure remains a major clinical challenge, underscoring the need to better understand post-infarction immune mechanisms and identify new therapeutic targets. Both innate and adaptive immunity contribute to adverse cardiac remodeling following myocardial infarction (MI), yet the role of cytotoxic cells such as natural killer (NK) cells remains poorly defined. Here, we show that after acute MI in mice, NK cells are recruited to the ischemic myocardium in a CCR2-dependent manner and become activated. Activated NK cells locally release granzyme B, promoting cardiomyocyte apoptosis, adverse ventricular remodeling, and impaired cardiac function. Genetic deletion or pharmacological depletion of NK cells reduces cardiomyocyte death, attenuates inflammation, limits myocardial injury, and improves cardiac function. In contrast, NK cell activation using an anti-NKG2A monoclonal antibody exacerbates ischemic heart failure. We further demonstrate that NK cells regulate bone marrow myelopoiesis through local GM-CSF production. Finally, we identify a distinct NK cellular and transcriptomic signature in human ischemic heart tissue at early stages. Together, these findings reveal a detrimental role for NK cells following acute MI and highlight NK cells as potential therapeutic targets to limit adverse cardiac remodeling.