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Cytotoxic CD8+ T cells promote granzyme B-dependent adverse post-ischemic cardiac remodeling

Author

Listed:
  • Icia Santos-Zas

    (Université de Paris, PARCC, INSERM)

  • Jeremie Lemarié

    (Université de Paris, PARCC, INSERM)

  • Ivana Zlatanova

    (Université de Paris, PARCC, INSERM)

  • Marine Cachanado

    (Assistance Publique-Hôpitaux de Paris, APHP.SU; Department of Clinical Pharmacology and Clinical Research Platform (URCEST-CRB-CRC-EST), Hôpital Saint Antoine)

  • Jean-Christophe Seghezzi

    (Service de cardiologie, Centre Hospitalier de Compiegne)

  • Hakim Benamer

    (Service de cardiologie, Institut Cardiovasculaire Paris Sud)

  • Pascal Goube

    (Service de cardiologie, Centre Hospitalier de Corbeil)

  • Marie Vandestienne

    (Université de Paris, PARCC, INSERM)

  • Raphael Cohen

    (Université de Paris, PARCC, INSERM)

  • Maya Ezzo

    (Université de Paris, PARCC, INSERM)

  • Vincent Duval

    (Université de Paris, PARCC, INSERM)

  • Yujiao Zhang

    (Université de Paris, PARCC, INSERM)

  • Jin-Bo Su

    (Inserm U955-IMRB, Equipe 03, UPEC, Ecole Nationale Vétérinaire d’Alfort)

  • Alain Bizé

    (Inserm U955-IMRB, Equipe 03, UPEC, Ecole Nationale Vétérinaire d’Alfort)

  • Lucien Sambin

    (Inserm U955-IMRB, Equipe 03, UPEC, Ecole Nationale Vétérinaire d’Alfort)

  • Philippe Bonnin

    (Inserm U965, Department of Physiology, Assistance Publique Hôpitaux de Paris)

  • Maxime Branchereau

    (Inserm U1048-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), université Paul Sabatier)

  • Christophe Heymes

    (Inserm U1048-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), université Paul Sabatier)

  • Corinne Tanchot

    (Université de Paris, PARCC, INSERM)

  • José Vilar

    (Université de Paris, PARCC, INSERM)

  • Clement Delacroix

    (Université de Paris, PARCC, INSERM)

  • Jean-Sebastien Hulot

    (Université de Paris, PARCC, INSERM)

  • Clement Cochain

    (Institute of Experimental Biomedicine, University Hospital Würzburg)

  • Patrick Bruneval

    (Université de Paris, PARCC, INSERM
    Service d’anatomopathologie, Hôpital Europeen G. Pompidou, Assistance Publique, Hôpitaux de Paris)

  • Nicolas Danchin

    (Service de cardiologie, Hôpital Europeen G. Pompidou, Assistance Publique, Hôpitaux de Paris)

  • Alain Tedgui

    (Université de Paris, PARCC, INSERM)

  • Ziad Mallat

    (Université de Paris, PARCC, INSERM
    Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke’s Hospital)

  • Tabassome Simon

    (Assistance Publique-Hôpitaux de Paris, APHP.SU; Department of Clinical Pharmacology and Clinical Research Platform (URCEST-CRB-CRC-EST), Hôpital Saint Antoine
    Sorbonne Université, UPMC-site St Antoine, Service de Pharmacologie, Assistance Publique-Hôpitaux de Paris, APHP.SU; Department of Clinical Pharmacology and Clinical Research Platform (URCEST-CRB-CRC-EST), Hôpital Saint Antoine)

  • Bijan Ghaleh

    (Inserm U955-IMRB, Equipe 03, UPEC, Ecole Nationale Vétérinaire d’Alfort)

  • Jean-Sébastien Silvestre

    (Université de Paris, PARCC, INSERM)

  • Hafid Ait-Oufella

    (Université de Paris, PARCC, INSERM
    Sorbonne Université, Service de médecine intensive-Réanimation, Assistance Publique, Hôpitaux de Paris)

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.

Suggested Citation

  • Icia Santos-Zas & Jeremie Lemarié & Ivana Zlatanova & Marine Cachanado & Jean-Christophe Seghezzi & Hakim Benamer & Pascal Goube & Marie Vandestienne & Raphael Cohen & Maya Ezzo & Vincent Duval & Yuji, 2021. "Cytotoxic CD8+ T cells promote granzyme B-dependent adverse post-ischemic cardiac remodeling," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21737-9
    DOI: 10.1038/s41467-021-21737-9
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    Cited by:

    1. Yasmin K. Alshoubaki & Bhavana Nayer & Yen-Zhen Lu & Ekaterina Salimova & Sin Nee Lau & Jean L. Tan & Daniela Amann-Zalcenstein & Peter F. Hickey & Gonzalo Monte-Nieto & Ajithkumar Vasanthakumar & Mik, 2024. "Tregs delivered post-myocardial infarction adopt an injury-specific phenotype promoting cardiac repair via macrophages in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Caihua Zhang & Kang Li & Hongzhang Zhu & Maosheng Cheng & Shuang Chen & Rongsong Ling & Cheng Wang & Demeng Chen, 2024. "ITGB6 modulates resistance to anti-CD276 therapy in head and neck cancer by promoting PF4+ macrophage infiltration," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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