Figure: The immunological mechanism of pattern recognition receptor Dectin-1 in myocardial ischemia/reperfusion injury.

With the support of National Natural Science Foundation of China (Project No. 81570316, 81400362), research team of Professor Ruiyan Zhang and Doctor Xiaoxiang Yan at Ruijin Hospital affiliated to Shanghai Jiaotong University, made important breakthrough in the study of immune response during myocardial ischemia/reperfusion injury. The results were recently published in Circulation on September 27, 2018, entitled “Dectin-1 contributes to myocardial ischemia-reperfusion injury by regulating macrophage polarization and neutrophil infiltration”. Xiaoxiang Yan from Ruijin Hospital is the corresponding author, while Qin Fan and Rong Tao are contributed equally as first authors. The website link is: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.036044.

 Acute myocardial infarction and ischemic cardiomyopathy have been critical risk factors threatening human health. Increasing number of percutaneous coronary intervention (PCI) results in reduced mortality, however, accompanying ischemia/reperfusion (IR) injury still seriously affects the prognosis. The research team focused on the role of immune response in myocardial IR injury, highlighting the accumulating macrophages and neutrophils during the acute phase. They first discovered that Dectin-1, a pattern recognition receptor mainly expressed on activated macrophages, is increased in the heart during the acute stage after IR injury, thought the RNA sequence analysis. Genetic ablation, antibody blockade, or Dectin-1 activation, along with bone marrow transfer chimeric model, were used to determine the functional role of Dectin-1 in the myocardial IR injury. They revealed that Dectin-1 could aggravate myocardial IR injury via inducing macrophage polarization toward the pro-inflammatory M1 phenotype as well as mediating the infiltration of Ly6C⁺ monocytes and neutrophils, thus leading to cardiomyocyte apoptosis and cardiac dysfunction. Furthermore, Dectin-1 contributed to neutrophil recruitment through the regulation of chemokines CXCL1 and G-CSF expression. In addition, Dectin-1-dependent IL-23/IL-1β production was shown to be essential for IL-17A expression by γδT cells, affecting the infiltration of neutrophils and myocardial IR injury. They also demonstrated that circulating Dectin-1⁺ monocyte levels were significantly higher in patients with ST-segment-elevation myocardial infraction than in control subjects, and positively correlated with the severity of cardiac dysfunction.

The study reveals a crucial role of the immunoregulatory receptor, Dectin-1, in the process of myocardial IR injury, and provides a novel potential therapeutic target for ischemic cardiomyopathy with clinical significance.