A critical role of CXCR6 in murine myocardial ischemia-reperfusion injury through activating IL-17a producing iNKT cells

作者：Wang, Shijun; Zhao, Gang; Zhang, Feng; Wu, Jian; Xu, Lei; Wang, Zhen; Yin, Peipei; Wang, Xingxu; You, Jieyun; Yang, Ji'e; Ge, Junbo^*; Zou, Yunzeng

来源：International Journal of Clinical and Experimental Pathology, 2016, 9(3): 3513-3520.

• CXCR6
• IL-17a
• iNKT cells
• ischemia/reperfusion

The pathologic role of invariant natural killer T (iNKT) cells in reperfusion injury after myocardial infarction remains elusive although they induce detrimental inflammatory response in hepatic and renal ischemia/reperfusion (I/R) injury. Here we suppress the activation of iNKT cells by knocking out the chemokine receptor, CXCR6, and investigate the precise role of iNKT cells in cardiac I/R injury. Our data indicate that cardiac infiltrated iNKT cells promote IL-17a secretion and IL-17a-dependent cell apoptosis. IL-17a mRNA and serum level are significantly lower in hearts from CXCR6(-/-) mice than in those from wild-type (WT) mice, and IL-17a producing iNKT cells are also less activated in CXCR6(-/-) mice. Further results confirm that CXCR6 deficiency-mediated cardiac protection against I/R injury is abolished by recombined IL-17a treatment. Left ventricular (LV) infarct size was significantly increased and LV ejection fraction (LVEF) reduced by rIL-17a in CXCR6(-/-) mice, as were decreased expression of Beclin-1 and increased expression of Bax. We therefore conclude that CXCR6 activation is required for myocardial infiltration of IL-17a producing iNKT cells after I/R injury. CXCR6 inhibition before reperfusion period may reduce infarct size and preserve cardiac function partly through attenuating the activity of IL-17a producing iNKT cells.

• 出版日期2016
• 单位复旦大学