Dynamic Profile of CD4 + T-Cell-Associated Cytokines/Chemokines following Murine Myocardial Infarction/Reperfusion

Dongsheng, Yuan, Jinjun, Tie, Zhican, Xu, Guanya, Liu, Xinyu, Ge, Zhulin, Wang, Xumin, Zhang, Shiyu, Gong, Gang, Liu, Qingshu, Meng, Fang, Lin, Zhongmin, Liu, Huimin, Fan, Xiaohui, Zhou

Mediators of Inflammation |

CD4 + T-cells play crucial roles in the injured heart. However, the way in which different CD4 + T subtypes function in the myocardial infarction/reperfusion (MI/R) heart is still poorly understood. We aimed to detect the dynamic profile of distinct CD4 + subpopulation-associated cytokines/chemokines by relying on a closed-chest acute murine MI/R model. The protein levels of 26 CD4 + T-cell-associated cytokines/chemokines were detected in the heart tissues and serum of mice at day 7 and day 14 post-MI/R or sham surgery. The mRNA levels of IL-4, IL-6, IL-13, IL-27, MIP-1 β , MCP-3, and GRO- α were measured in blood mononuclear cells. The protein levels of IL-4, IL-6, IL-13, IL-27, MIP-1 β , MCP-3, and GRO- α increased in both injured heart tissues and serum, while IFN- γ , IL-12P70, IL-2, IL-1 β , IL-18, TNF- α , IL-5, IL-9, IL-17A, IL-23, IL-10, eotaxin, MIP-1 α , RANTES, MCP-1, and MIP-2 increased only in MI/R heart tissues in the day 7 and day 14 groups compared to the sham group. In serum, the IFN- γ , IL-23, and IL-10 levels were downregulated in the MI/R model at both day 7 and day 14 compared to the sham. Compared with the protein expressions in injured heart tissues at day 7, IFN- γ , IL-12P70, IL-2, IL-18, TNF- α , IL-6, IL-4, IL-5, IL-9, IL-17A, IL-23, IL-27, IL-10, eotaxin, IP-10, RANTES, MCP-1, MCP-3, and GRO- α were reduced, while IL-1 β and MIP-2 were elevated at day 14. IL-13 and MIP-1 β showed higher levels in the MI/R serum at day 14 than at day 7. mRNA levels of IL-4, IL-6, IL-13, and IL-27 were increased in the day 7 group compared to the sham, while MIP-1 β , MCP-3, and GRO- α mRNA levels showed no significant difference between the MI/R and sham groups in blood mononuclear cells. Multiple CD4 + T-cell-associated cytokines/chemokines were upregulated in the MI/R hearts at the chronic stage. These results provided important evidence necessary for developing future immunomodulatory therapies after MI/R.