NK cells promote cardiac cell death and regulate myelopoiesis in myocardial infarction.
Publisher DOI
PubMed ID
41922374
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.
Date Issued
2026-04-01
Publication Type
Article
Subject(s)
Language(s)
en
Author(s)
Cohen, Raphael | |
Duval, Vincent | |
Al-Rifai, Rida | |
Maryam, Sidrah | |
Santos-Zas, Icia | |
Braik, Rayan | |
Diedisheim, Marc | |
Jouve, Charlène | |
Nicoletti, Simon | |
Thietart, Sara | |
Guyon, Théo | |
Chetrit, Luna | |
Kral, Maria | |
Loupy, Alexandre | |
Domenge, Orianne | |
Livrozet, Marine | |
Hulot, Jean-Sebastien | |
Sakalli, Ecem T | |
Rizzo, Giuseppe | |
Saliba, Antoine-Emmanuel | |
Piollet, Marie | |
Bruneval, Patrick | |
Tedgui, Alain | |
Taleb, Soraya | |
Hermine, Olivier | |
Wicks, Ian | |
Silvestre, Jean-Sébastien | |
Hayat, Sikander | |
Cochain, Clement | |
Vivier, Eric | |
Ait-Oufella, Hafid |
Journal
Nature Communications
Publisher
Nature Research
ISSN
2041-1723
Related Collection(s)
Access(Rights)
open.access