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

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.

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Publication Details

Journal
Open Access CRIS of the University of Bern
Published
2026-04-01
DOI
https://doi.org/10.48620/96733
Primary Topic
Cardiac Fibrosis and Remodeling
Type
article
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article

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

Charlène Jouve, Soraya Taleb, Rayan Braik, Éric Vivier et al.
Open Access CRIS of the University of Bern
Cardiac Fibrosis and Remodeling
article

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

Charlène Jouve, Soraya Taleb, Rayan Braik, Éric Vivier, Clément Cochain, Patrick Bruneval, Orianne Domengé, Sidrah Maryam, Marie Piollet, Sara Thietart, Rida Al-Rifai, Marine Livrozet, Marc Diedisheim, Maria Kral, Ecem T. Sakalli, Alain Tedgui, Alexandre Loupy, Yvonne Döring, Raphael M. Cohen, Olivier Hermine, Simon Nicoletti, Vincent Duval, Ian P. Wicks, Théo Guyon, Luna Chetrit, Jean-Sebastien Silvestre, Hafid Ait-Oufella, Icia Santos-Zas, Sikander Hayat, Christian Weber, Jean-Sebastien Hulot, Giuseppe Rizzo, Antoine-Emmanuel Saliba
article en

Abstract

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.

Open Access CRIS of the University of Bern
Universitätsklinik für Neurologie (AT)
Good health and well-being
Openalex Percentile: Top 25%
Cardiac Fibrosis and Remodeling
DOIOpen Access PDFOpenAlex
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