| Title: |
Cytotoxic CD8 + T cells promote granzyme B-dependent adverse post-ischemic cardiac remodeling |
| Authors: |
Santos-Zas, Icia; Lemarié, Jeremie; Zlatanova, Ivana; Cachanado, Marine; Seghezzi, Jean-Christophe; Benamer, Hakim; Goube, Pascal; Vandestienne, Marie; Cohen, Raphael; Ezzo, Maya; Duval, Vincent; Zhang, Yujiao; Su, Jin-Bo; Bizé, Alain; Sambin, Lucien; Bonnin, Philippe; Branchereau, Maxime; Heymes, Christophe; Tanchot, Corinne; Vilar, José; Delacroix, Clement; Hulot, Jean-Sebastien; Cochain, Clement; Bruneval, Patrick; Danchin, Nicolas; Tedgui, Alain; Mallat, Ziad; Simon, Tabassome; Ghaleh, Bijan; Silvestre, Jean-Sébastien; Ait-Oufella, Hafid |
| Publisher Information: |
Nature Publishing Group UK; Nature Communications |
| Publication Year: |
2021 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
Article; /631/250/1619; /692/4019/592/75/230; /13; /13/1; /13/2; /13/21; /13/31; /13/51; /13/106 |
| Description: |
Funder: ANR-16-CE14-0016 ; Abstract: Acute myocardial infarction is a common condition responsible for heart failure and sudden death. Here, we show that following acute myocardial infarction in mice, 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. Depletion of CD8+ T lymphocytes decreases apoptosis within the ischemic myocardium, hampers inflammatory response, limits myocardial injury and improves heart function. These effects are recapitulated in mice with Granzyme B-deficient CD8+ T cells. The protective effect of CD8 depletion on heart function is confirmed by using a model of ischemia/reperfusion in pigs. Finally, we reveal that elevated circulating levels of GRANZYME B in patients with acute myocardial infarction predict increased risk of death at 1-year follow-up. Our work unravels a deleterious role of CD8+ T lymphocytes following acute ischemia, and suggests potential therapeutic strategies targeting pathogenic CD8+ T lymphocytes in the setting of acute myocardial infarction. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf; application/zip; text/xml |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/318444 |
| DOI: |
10.17863/CAM.65558 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/318444; https://doi.org/10.17863/CAM.65558 |
| Rights: |
Attribution 4.0 International (CC BY 4.0) ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.47E511F7 |
| Database: |
BASE |