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Circulation. 2019 Jan 29;139(5):663-678. doi: 10.1161/CIRCULATIONAHA.118.036044.

Dectin-1 Contributes to Myocardial Ischemia/Reperfusion Injury by Regulating Macrophage Polarization and Neutrophil Infiltration.

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Departments of Cardiology (Q.F., R.T., H.Z., H.X., L.L., J.H., Q.Z., W.S., R.Z., X.Y.), Shanghai Jiaotong University School of Medicine, PR China.
Rui Jin Hospital, and Institute of Cardiovascular Diseases (Q.F., H.Z., H.X., L.L., Q.C., R.Z., X.Y.), Shanghai Jiaotong University School of Medicine, PR China.
Pathology (T.W.), Shanghai Jiaotong University School of Medicine, PR China.
Institute of Clinical Pathology, Department of Pathology, Shantou University Medical College, Guangdong, PR China (M.S.).
Division of Experimental Animal Immunology, Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan (Y.I.).



Macrophage-associated immune response plays an important role in myocardial ischemia/reperfusion (IR) injury. Dectin-1, expressed mainly on activated myeloid cells, is crucial for the regulation of immune homeostasis as a pattern recognition receptor. However, its effects and roles during the myocardial IR injury remain unknown.


Genetic ablation, antibody blockade, or Dectin-1 activation, along with the adoptive bone marrow transfer chimeric model, was used to determine the functional significance of Dectin-1 in myocardial IR injury. Immune cell filtration and inflammation were examined by flow cytometry, quantitative real-time polymerase chain reaction, and immunohistochemistry. Moreover, Dectin-1+ cells were analyzed by flow cytometry in the blood of patients with ST-segment-elevation myocardial infarction and stable patients with normal coronary artery (control).


We demonstrated that Dectin-1 expression observed on the bone marrow-derived macrophages is increased in the heart during the early phase after IR injury. Dectin-1 deficiency and antibody-mediated Dectin-1 inhibition led to a considerable improvement in cardiac function, accompanied by a reduction in cardiomyocyte apoptosis, which was associated with a decrease in M1 macrophage polarization and Ly-6C+ monocyte and neutrophil infiltration. Activation of Dectin-1 with its agonist had the opposite effects. Furthermore, Dectin-1 contributed to neutrophil recruitment through the regulation of Cxcl1 and granulocyte colony-stimulating factor expression. In addition, Dectin-1-dependent interleukin-23/interleukin-1β production was shown to be essential for interleukin-17A expression by γδT cells, leading to neutrophil recruitment and myocardial IR injury. Furthermore, we demonstrated that circulating Dectin-1+CD14++CD16- and Dectin-1+CD14++CD16+ monocyte levels were significantly higher in patients with ST-segment-elevation myocardial infarction than in controls and positively correlated with the severity of cardiac dysfunction.


Our results reveal a crucial role of Dectin-1 in the process of mouse myocardial IR injury and provide a new, clinically significant therapeutic target.


chemokines; immune; macrophages; reperfusion injury; system

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