Single-Cell Multi-Omics Identifies Specialized Cytotoxic and Migratory CD8 + Effector T Cells in Acute Myocarditis

作者：Zhonghua Tong, Xiangyu Yan, Tao Chen, Weijun Song, Di Su, Naixin Wang, Yafei Zhang, Yingjin Kong, Dong-Ni Wang, P Wang, Yujia Chen, Xiaoqi Wang, Jing Cui, Jiayu Sui, Shuang Liu, Yanping Li, Qiannan Yang, Zi‐Qi Zheng, Zexi Jin, Yunling Li, Fang Liu, Jiaxuan Li, Lishuang Qi, Jiaxing Deng, Zhaoying Li, Shuang Yang, Haibo Jia, Yong Ji, Maomao Zhang, Bo Yu · 发表于：Circulation · 年份：2025 · DOI：10.1161/circulationaha.125.073836 · 被引用次数：10 · 研究领域：Viral Infections and Immunology Research、Cardiac Fibrosis and Remodeling、Atherosclerosis and Cardiovascular Diseases

BACKGROUND: Acute myocarditis (AM), particularly fulminant myocarditis (FM), is an infrequent but life-threatening cardiac inflammation, with limited effective precision-targeted treatments available. This urgent clinical challenge has prompted further investigations into the mechanisms underlying this pathology to develop novel therapeutic approaches. METHODS: We enrolled 40 patients diagnosed with AM (24 mild, 16 fulminant) between December 2022 and November 2023. Using a multi-omics approach, we analyzed peripheral blood mononuclear cells and plasma, integrating single-cell RNA sequencing, single-cell T-cell receptor sequencing, cytometry by time of flight, and Olink proteomics to identify specific pathogenic immune subsets and molecular alterations. In vitro experiments validated the function and inducing signals of identified pathogenic subsets. In coxsackievirus B3–induced FM mice, cytometry by time of flight analysis was performed on peripheral blood mononuclear cells and cardiac infiltrating immune cells. Pharmacological blockade of key molecules was tested to assess potential therapeutic efficacy. RESULTS: We identified that a specialized type of CD8 + effector T cells, CD57 + CD8 + T cells with high cytotoxicity and migration potential, were substantially enriched and exhibited large clonal expansion in AM. Differential expression analysis revealed upregulation of natural killer–like receptor genes in CD57 + CD8 + effector T cells from FM compared with mild cases, w...