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.
Authors
- Charlène Jouve (ORCID: https://orcid.org/0000-0002-5792-4621)
- Soraya Taleb (ORCID: https://orcid.org/0000-0002-6650-619X)
- P. Bruneval
- Rayan Braik
- Éric Vivier (ORCID: https://orcid.org/0000-0001-7022-8287)
- Clément Cochain (ORCID: https://orcid.org/0000-0002-0340-1745)
- Orianne Domengé (ORCID: https://orcid.org/0000-0003-2395-3552)
- Sidrah Maryam
- Marie Piollet (ORCID: https://orcid.org/0000-0002-2025-6594)
- Sara Thietart (ORCID: https://orcid.org/0000-0002-1137-7247)
- Rida Al-Rifai (ORCID: https://orcid.org/0000-0002-6976-0011)
- Marine Livrozet
- Marc Diedisheim (ORCID: https://orcid.org/0000-0002-0418-1107)
- Maria Kral
- Ecem T. Sakalli (ORCID: https://orcid.org/0000-0001-5121-9369)
- Alexandre Loupy (ORCID: https://orcid.org/0000-0003-3388-7747)
- Raphael M. Cohen (ORCID: https://orcid.org/0000-0001-6722-3936)
- Olivier Hermine (ORCID: https://orcid.org/0000-0003-2574-3874)
- Jean‐Sébastien Hulot (ORCID: https://orcid.org/0000-0001-5463-6117)
- Simon Nicoletti
- Vincent Duval (ORCID: https://orcid.org/0009-0008-0138-7258)
- Ian P. Wicks (ORCID: https://orcid.org/0000-0001-7050-6822)
- Théo Guyon
- Luna Chetrit
- Jean-Sebastien Silvestre
- Hafid Ait-Oufella
- Icia Santos-Zas
- C Weber
- Alain Tedgui
- Yvonne Döring
- Antoine-Emmanuel Saliba
- Sikander Hayat
- Giuseppe Rizzo
Institutions
- University of Bern (CH)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Université Paris Cité (FR)
- Aix-Marseille Université (FR)
- University of Würzburg (DE)
- Maastricht University Medical Centre (NL)
- University Hospital of Bern (CH)
- Sorbonne Université (FR)
- Institut Necker Enfants Malades (FR)
- Sorbonne Paris Cité (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Hôpital Européen Georges-Pompidou (FR)
- Munich Cluster for Systems Neurology (DE)
- Helmholtz Institute for RNA-based Infection Research (DE)
- Universitätsklinikum Würzburg (DE)
- German Centre for Cardiovascular Research (DE)
- Paris Cardiovascular Research Center (FR)
- Centre d’Immunologie de Marseille-Luminy (FR)
- Instituto de Investigación Sanitaria de Santiago (ES)
- Ludwig-Maximilians-Universität München (DE)
- RWTH Aachen University (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1038/s41467-026-71334-x
- Primary Topic
- Cardiac Fibrosis and Remodeling
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Agence Nationale de la Recherche