Hu Zhan, Hua Xiumeng, Mo Xiuxue, Chang Yuan, Chen Xiao, Xu Zhenyu, Tao Mengtao, Hu Gang, Song Jiangping
Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, National Centre for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
Department of Cardiovascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
iScience. 2023 Jun 16;26(7):107162. doi: 10.1016/j.isci.2023.107162. eCollection 2023 Jul 21.
Giant cell myocarditis (GCM) is a rare, usually rapidly progressive, and potentially fatal disease. Detailed inflammatory responses remain unknown, in particular the formation of multinucleate giant cells. We performed single-cell RNA sequencing analysis on 15,714 cells extracted from the hearts of GCM rats and normal rats. NETosis has been found to contribute to the GCM process. An inhibitor of NETosis, GSK484, alleviated GCM inflammation . (a marker of neutrophils) and (a marker of NETosis) were expressed at higher levels in patients with GCM than in patients with DCM and healthy controls. Imaging mass cytometry analysis revealed that immune cell types within multinucleate giant cells included CD4 T cells, CD8 T cells, neutrophils, and macrophages but not B cells. We elucidated the role of NETosis in GCM pathogenesis, which may serve as a potential therapeutic target in the clinic.
巨细胞性心肌炎（GCM）是一种罕见的、通常进展迅速且可能致命的疾病。详细的炎症反应仍不清楚，尤其是多核巨细胞的形成。我们对从GCM大鼠和正常大鼠心脏中提取的15714个细胞进行了单细胞RNA测序分析。已发现中性粒细胞胞外陷阱形成（NETosis）有助于GCM进程。NETosis抑制剂GSK484减轻了GCM炎症。（中性粒细胞标志物）和（NETosis标志物）在GCM患者中的表达水平高于扩张型心肌病（DCM）患者和健康对照。成像质谱流式细胞术分析显示，多核巨细胞内的免疫细胞类型包括CD4 T细胞、CD8 T细胞、中性粒细胞和巨噬细胞，但不包括B细胞。我们阐明了NETosis在GCM发病机制中的作用，这可能成为临床上潜在的治疗靶点。
