Activation of CXCL16/CXCR6 axis aggravates cardiac ischemia/reperfusion injury by recruiting the IL-17a-producing CD1d + T cellsDear Editor, Reperfusion is commonly used for the treatment of acute myocardial infarction, but inflammation-related reperfusion injury limits its clinical application. Blockade of IL-17a is considered one of the effective therapies for myocardial ischemia/reperfusion (I/R) injury. 1 However, the generation of cardiac IL-17a and the subpopulations of IL-17aproducing cells remain obscure. In the present study, we reveal that the CXCL16/CXCR6 signal axis plays a key role in IL-17a production and cardiac reperfusion inflammation in a mouse model of cardiac I/R injury.CXCL16 is a proinflammatory chemokine that widely expressed in endothelial cells, vascular smooth muscle cells, and fibroblasts. 2 CXCL16 is a novel diagnostic hallmark of acute coronary syndrome, 3,4 and CXCL16 is essential for the migration and recruitment of IL-17a-producing T cells to the atherosclerotic lesions. 5 After myocardial ischemia for 40 min, we observed that the protein level of CXCL16 increased rapidly in the left ventricle (LV) of mice at 2 h after reperfusion and maintained high level during the reperfusion period (Figure 1A). With the highest abundance, CXCL16 in the heart stood out among those in the other organs after I/R (Figure 1B), suggesting that myocardial I/R-induced CXCL16 activation was cardiac specific. Moreover, we examined the transcriptional levels of a number of proinflammatory chemokines and their receptors in mouse heart with I/R stress. Compared with other chemokines, the mRNA levels of CXCL16, CCL5, CXCL1, and CXCR2 were significant upregulated after I/R (Figure S1A).To investigate the precise role of CXCL16 in cardiac I/R injury, we knocked down the endogenous CXCL16 by delivering adenovirus-shRNA targeting CXCL16 gene 24 h before I/R injury (Figure S1B). The results showed that cardiac IL-17a production (Figure 1C) and cell apoptosis were significantly attenuated in CXCL16-deficient mice compared with those in wild-type (WT) mice (Figure 1D and E). The severity of myocardial lesion is evaluated by twoThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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