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

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

doi:10.1155/2019/9483647

Abstract

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-1β, MCP-3, and GRO-α were measured in blood mononuclear cells. The protein levels of IL-4, IL-6, IL-13, IL-27, MIP-1β, MCP-3, and GRO-α increased in both injured heart tissues and serum, while IFN-γ, IL-12P70, IL-2, IL-1β, IL-18, TNF-α, IL-5, IL-9, IL-17A, IL-23, IL-10, eotaxin, MIP-1α, 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-1β and MIP-2 were elevated at day 14. IL-13 and MIP-1β 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-1β, 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.

Highlights

Ischemic heart diseases remained the leading cause of death worldwide in the last decade [1]
MIP-1β, MCP-3, and GRO-α mRNA levels showed no significant difference between the myocardial infarction/reperfusion (MI/R) and control groups (Figures 9(e)–9(g))
The present study provides a comprehensive analysis of the temporal dynamics of CD4+ T-cell-related cytokines/ chemokines in injured heart tissues and serum in the murine acute myocardial infarction/reperfusion (AMI/R) model

Summary

Introduction

Ischemic heart diseases remained the leading cause of death worldwide in the last decade [1]. Multiple mechanisms, including progressive apoptosis of myocardial cells, neurohumoral activation, and oxidative stress, contribute to the activation of innate immune responses, initiate a cascade inflammatory reaction, and lead to deterioration, which results in scar formation and ventricle dilation remodeling [4, 5]. CD4+ regulatory T cells (Treg cells), serving as a brake, can block excessive inflammation and tissue destruction [14, 15]. These T helper subsets orchestrate to tune immune homeostasis, and the disturbance of the balance of these cells leads to inflammatory disease and tissue destruction

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Conclusion