B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction
Sage, Andrew P
Charo, Israel F
Binder, Christoph J
Tedder, Thomas F
Nature Publishing Group
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Zouggari, Y., Ait-Oufella, H., Bonnin, P., Simon, T., Sage, A. P., Guérin, C., Vilar, J., et al. (2013). B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Nature Medicine, 19 1273-1280. https://doi.org/10.1038/nm.3284
Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that following acute MI in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6Chi monocyte mobilization and recruitment, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff-r deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impedes Ccl7 production and monocyte mobilization, limits myocardial injury and improves heart function. These effects are recapitulated in mice with B cell selective Ccl7 deficiency. We also show that elevated circulating levels of Ccl7 and Baff in patients with acute MI predict increased risk of death or recurrent MI at follow-up. The work unravels a previously unsuspected interaction between mature B lymphocytes and monocytes following acute ischemia, and identifies novel therapeutic targets for this devastating condition.
This work was supported by Inserm, British Heart Foundation (Z.M.), European Research Council (Z.M.), Fondation Coeur et Recherche (Z.M., T.S., N.D.), Fondation pour la Recherche Medicale (J.S.S.), European Union Seven Framework programme TOLERAGE (Z.M.), Fondation Leducq transatlantic network (C.J.B., D.T., A.T., J.S.S., Z.M.), National Institutes of Health grants AI56363 and AI057157, and a grant from The Lymphoma Research Foundation (T.F.T).
British Heart Foundation (PG/11/107/29236)
External DOI: https://doi.org/10.1038/nm.3284
This record's URL: https://www.repository.cam.ac.uk/handle/1810/260338