首页|Single-cell profile reveals the landscape of cardiac immunity and identifies a cardio-protective Ym-1hi neutrophil in myocardial ischemia-reperfusion injury

Single-cell profile reveals the landscape of cardiac immunity and identifies a cardio-protective Ym-1hi neutrophil in myocardial ischemia-reperfusion injury

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Myocardial ischemia-reperfusion injury(MIRI)is a major hindrance to the success of cardiac reperfusion therapy.Although increased neutrophil infiltration is a hallmark of MIRI,the subtypes and alterations of neutrophils in this process remain unclear.Here,we performed single-cell sequencing of cardiac CD45+cells isolated from the murine myocardium subjected to MIRI at six-time points.We identified diverse types of infiltrating immune cells and their dynamic changes during MIRI.Cardiac neutrophils showed the most immediate response and largest changes and featured with functionally heterogeneous subpop-ulations,including Ccl3hi Neu and Ym-1hi Neu,which were increased at 6 h and 1 d after reperfusion,respectively.Ym-1hi Neu selectively expressed genes with protective effects and was,therefore,identified as a novel specific type of cardiac cell in the injured heart.Further analysis indicated that neutrophils and their subtypes orchestrated subsequent immune responses in the cardiac tissues,especially instructing the response of macrophages.The abundance of Ym-1hi Neu was closely correlated with the therapeutic efficacy of MIRI when neutrophils were specifically targeted by anti-Lymphocyte antigen 6 complex locus G6D(Ly6G)or anti-Intercellular cell adhesion molecule-1(ICAM-1)neutralizing antibodies.In addition,a neutrophil subtype with the same phenotype as Ym-1hi Neu was detected in clinical samples and corre-lated with prognosis.Ym-1 inhibition exacerbated myocardial injury,whereas Ym-1 supplementation significantly ameliorated injury in MIRI mice,which was attributed to the tilt of Ym-1 on the polarization of macrophages toward the repair phenotype in myocardial tissue.Overall,our findings reveal the anti-inflammatory phenotype of Ym-1hi Neu and highlight its critical role in myocardial protection during the early stages of MIRI.

Myocardial ischemia-reperfusion injuryNeutrophilYm-1Cardiac immune responseSingle-cell sequencing

Yalan Dong、Zhenyu Kang、Zili Zhang、Yongqiang Zhang、Haifeng Zhou、Yanfei Liu、Xinxin Shuai、Junyi Li、Liangqingqing Yin、Xunxun Wang、Yan Ma、Heng Fan、Feng Jiang、Zhihao Lin、Congzhu Ding、Kim Yun Jin、Alexey Sarapultsev、Fangfei Li、Ge Zhang、Tian Xie、Changjun Yin、Xiang Cheng、Shanshan Luo、Yue Liu、Desheng Hu

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Department of Integrated Traditional Chinese and Western Medicine,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China

Hubei Key Laboratory of Biological Targeted Therapy,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China

Nanjing Drum Tower Hospital,Clinical College of Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing 210008,China

National Clinical Research Center for Chinese Medicine Cardiology,Xiyuan Hospital,Chinese Academy of Chinese Medical Sciences,Beijing 100091,China

Department of Cardiology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China

Department of International Education,Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China

Institute of Neuroscience,School of Medicine,Xiamen University,Xiamen 361102,China

School of Traditional Chinese Medicine,Xiamen University Malaysia,Sepang 43900,Malaysia

School of Medical Biology,South Ural State University,Chelyabinsk 620049,Russia

Shum Yiu Foon Sum Bik Chuen Memorial Centre for Cancer and Inflammation Research(CCIR),School of Chinese Medicine,Hong Kong Baptist University,Hong Kong 999077,China

Institute of Integrated Bioinfomedicine and Translational Science,School of Chinese Medicine,Hong Kong Baptist University,Hong Kong 999077,China

Division of Vascular Surgery,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China

Institute of Precision Medicine,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China

Institute for Cardiovascular Prevention(IPEK),Ludwig-Maximilians-University,Munich 80336,Germany

Institute of Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China

China-Russia Medical Research Center for Stress Immunology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaPostdoctoral Science Foundation of ChinaPostdoctoral Science Foundation of ChinaFoundation of Hubei Key Laboratory of Biological Targeted Therapy

82022076819742498207013682104488823051942023M7312222020T130040ZX2023swbx021

2024

10.1016/j.scib.2024.02.003

科学通报(英文版)
中国科学院

科学通报(英文版)

CSTPCD
ISSN：1001-6538
年,卷(期)：2024.69(7)
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