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

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.

Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice

“…Thus, IL-9 may be the novel contributing factor in atherosclerosis [16][17][18]. Recent studies also reported that Th9/IL-9 levels were increased in patients with aortic dissection and in myocardial infarction/reperfusion mice [19,20]. In coxsackievirus B3-induced myocarditis, IL-9 reduces viral replication and thus reduces myocardial injury [21].…”

Myocardial ischemia‐reperfusion induced cardiac extracellular vesicles harbour proinflammatory features and aggravate heart injury

“…Inhibition of the proinflammatory EVs during IR helps break the inflammation‐injury circle and eventually alleviate the cardiac injury. In addition to local inflammation induced by direct cardiac injury, it is still a mystery that heart disease is usually accompanied by a systemic low‐grade inflammation (Scally et al., 2019; Yuan et al., 2019). As shown in our study, IR injury not only increased the inflammation in the heart but also in distant organs, and GW4869 treatment dampened the systemic inflammation in IR mice.…”

Interleukin‐9‐secreting CD4+ T cells regulate CD8+ T cells cytotoxicity in patients with acute coronary syndromes

“…Activated T cells were elevated in patients with UAP and AMI compared with SAP, suggesting that T‐cell immunity may be involved in the mechanisms of coronary instability (6). CD8 + T cells are accumulated and activated in the necrotic myocardium of AMI and contributed to myocardial injury (7, 8), while CD4 + T cells also play modulatory roles in injury and healing post‐myocardial infarction via secretion of associated cytokines (9, 10).…”