Viral myocarditis (VMC) is a cardiac disease associated with myocardial inflammation and injury induced by virus infection. Cardiomyocytes have recently been regarded as key players in eliciting and modulating inflammation within the myocardium. Kruppel-like factor 10 (KLF10) is a crucial regulator of various pathological processes and plays different roles in a variety of diseases. However, its role in VMC induced by coxsackievirus B3 (CVB3) infection remains unknown. In this study, we report that cardiac KLF10 confers enhanced protection against viral myocarditis. We found that KLF10 expression was downregulated upon CVB3 infection. KLF10 deficiency enhanced cardiac viral replication and aggravated VMC progress. Bone marrow chimera experiments indicated that KLF10 expression in nonhematopoietic cells was involved in the pathogenesis of VMC. We further identified MCP-1 as a novel target of KLF10 in cardiomyocytes, and KLF10 cooperated with histone deacetylase 1 (HDAC1) to negatively regulate MCP-1 expression by binding its promoter, leading to activation of MCP-1 transcription and recruitment of Ly6C^high monocytes/macrophages into the myocardium. This novel mechanism of MCP-1 regulation by KLF10 might provide new insights into the pathogenesis of VMC and a potential therapeutic target for VMC.

病毒性心肌炎（VMC）是一种与病毒感染引起的心肌炎症和损伤相关的心脏病。心肌细胞最近被认为是引发和调节心肌内炎症的关键因素。Kruppel 样因子 10 (KLF10) 是各种病理过程的关键调节因子，在多种疾病中发挥着不同的作用。然而，其在柯萨奇病毒 B3 (CVB3) 感染诱导的 VMC 中的作用仍然未知。在这项研究中，我们报告心脏 KLF10 增强了对病毒性心肌炎的保护作用。我们发现 KLF10 表达在 CVB3 感染后下调。KLF10 缺乏增强心脏病毒复制并加重 VMC 进展。骨髓嵌合体实验表明KLF10在非造血细胞中的表达参与了VMC的发病机制。^高单核细胞/巨噬细胞进入心肌。这种 KLF10 调控 MCP-1 的新机制可能为 VMC 的发病机制和 VMC 的潜在治疗靶点提供新的见解。