TREKING: TaRgEting NK cells in post-Ischemic cardiac remodeliNG

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Acute myocardial infarction is a common condition responsible for heart failure and sudden death. We precedently showed that CD8+ T lymphocytes are recruited and activated in the ischemic heart tissue and release Granzyme B, leading to cardiomyocyte apoptosis, adverse ventricular remodeling and deterioration of myocardial function. NK cells, belonging to innate immunity cells are playing an important role in anti-viral and anti-tumor immunity. These cells release also Granzyme B and secrete IFNg, TNFa and GM-CSF. The goal of this study was to unravel the distinct role of NK cells in post-ischemic injury. Acute MI was induced in mice by permanent ligation of the left anterior descending coronary artery. Cardiac function and remodeling were assessed by using echocardiography and histology. To determine the specific role of NK cells, the study used mice with and without NK cell depletion but also with and without hyperactivation of these NK cells. We assessed cardiac NK cells and innate populations using flow cytometry and RNA sequencing. We found that NK cells levels were increased in the heart after experimental MI. Depletion of NK cells restored cardiac function whereas hyperactivation of these cells via anti-NKG2A antibody showed worst cardiac function and left ventricle remodeling. Co cultured NK cells with cardiomycoytes showed apoptosis via Granzyme B. NK cells depletion by anti-NK1.1 antibody decreased monocyte recruitment after MI leading to anti-inflammatory environment permitting a less adverse post-ischemic cardiac remodeling. NK cells altered cardiac healing and aggravate the recovery of heart function after MI in mice. Depletion of NK cells could be a novel therapeutic strategy to promote a reparative response after MI.