Xie Fei, Li Junquan
Department of Cardiac Surgery, The Second Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang, China.
Medicine (Baltimore). 2025 Jun 27;104(26):e43033. doi: 10.1097/MD.0000000000043033.
Viral myocarditis (VMC), a multifaceted pathological condition predominantly triggered by viral infections, has emerged as a major worldwide healthcare concern due to its intricate pathogenesis and substantial disease burden. Although the centrality of immune dysregulation in driving VMC progression is well-established, the precise identities of distinct immune cell subsets and their molecular mediators governing pathological progression continue to present significant knowledge gaps. Single-cell datasets were integrated using quality control, batch correction, and normalization. The FindAllMarkers function identified marker genes for each cluster. Cell types were annotated based on literature-derived marker genes. DESeq2 was employed to identify differentially expressed genes in T cells. CellChat was used to explore intercellular communication and identify key ligand-receptor signaling pathways. Receiver operating characteristic curves assessed the predictive performance of key factors in a validation cohort. T cells were re-annotated for higher-resolution subtyping, and pseudotime analysis depicted the cell trajectories of T cell subtypes. Integrated single-cell data revealed a comprehensive single-cell atlas of VMC. Mechanistic delineation of T cell as principal pathogenic effectors emerged through multi-omics interrogation incorporating single-cell transcriptomic profiling and pathological trajectory reconstruction; functional genomics analyses further substantiated their cardinal involvement in cardiotropic viral pathogenesis. Additionally, communication analysis highlighted CCL as a critical immune regulatory pathway for T cell interactions in VMC. Significant upregulation of CCL3 was confirmed in the validation cohort, establishing it as a potential biomarker and therapeutic target for VMC. Pseudotime analysis and re-annotation of T cell subpopulations revealed significant enrichment of T.8EFF.OT1LISO and T.Tregs in VMC. This study identifies T cells as key immune players in VMC, with CCL3 proposed as a novel biomarker for the condition.
病毒性心肌炎（VMC）是一种主要由病毒感染引发的多方面病理状况，由于其复杂的发病机制和巨大的疾病负担，已成为全球主要的医疗保健问题。尽管免疫失调在推动VMC进展中的核心作用已得到充分确立，但不同免疫细胞亚群及其控制病理进展的分子介质的确切身份仍然存在重大知识空白。使用质量控制、批次校正和归一化方法对单细胞数据集进行整合。FindAllMarkers函数识别每个簇的标记基因。根据文献来源的标记基因对细胞类型进行注释。使用DESeq2识别T细胞中差异表达的基因。使用CellChat探索细胞间通讯并识别关键的配体-受体信号通路。通过受试者工作特征曲线评估验证队列中关键因素的预测性能。对T细胞进行重新注释以实现更高分辨率的亚型分类，伪时间分析描绘了T细胞亚型的细胞轨迹。整合的单细胞数据揭示了VMC的综合单细胞图谱。通过结合单细胞转录组分析和病理轨迹重建的多组学研究，明确了T细胞作为主要致病效应器的机制；功能基因组学分析进一步证实了它们在嗜心性病毒发病机制中的核心作用。此外，通讯分析突出了CCL作为VMC中T细胞相互作用的关键免疫调节途径。在验证队列中证实CCL3显著上调，将其确立为VMC的潜在生物标志物和治疗靶点。T细胞亚群的伪时间分析和重新注释显示VMC中T.8EFF.OT1LISO和T.Tregs显著富集。本研究确定T细胞是VMC中的关键免疫参与者，提出CCL3作为该疾病的新型生物标志物。
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