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

Yalan Dong ¹Zhenyu Kang ²Zili Zhang ²Yongqiang Zhang ³Haifeng Zhou ²Yanfei Liu ⁴Xinxin Shuai ⁵Junyi Li ²Liangqingqing Yin ²Xunxun Wang ²Yan Ma ²Heng Fan ²Feng Jiang ⁶Zhihao Lin ⁷Congzhu Ding ³Kim Yun Jin ⁸Alexey Sarapultsev ⁹Fangfei Li ¹⁰Ge Zhang ¹¹Tian Xie ⁵Changjun Yin ¹²Xiang Cheng ¹³Shanshan Luo ¹⁴Yue Liu ⁴Desheng Hu¹⁵

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作者信息

1. 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
2. Department of Integrated Traditional Chinese and Western Medicine,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China
3. Nanjing Drum Tower Hospital,Clinical College of Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing 210008,China
4. National Clinical Research Center for Chinese Medicine Cardiology,Xiyuan Hospital,Chinese Academy of Chinese Medical Sciences,Beijing 100091,China
5. Department of Cardiology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China
6. Department of International Education,Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China
7. Institute of Neuroscience,School of Medicine,Xiamen University,Xiamen 361102,China
8. School of Traditional Chinese Medicine,Xiamen University Malaysia,Sepang 43900,Malaysia
9. School of Medical Biology,South Ural State University,Chelyabinsk 620049,Russia
10. 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
11. Institute of Integrated Bioinfomedicine and Translational Science,School of Chinese Medicine,Hong Kong Baptist University,Hong Kong 999077,China
12. 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
13. Hubei Key Laboratory of Biological Targeted Therapy,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;Department of Cardiology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China
14. Institute of Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China
15. 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;China-Russia Medical Research Center for Stress Immunology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China
折叠

Abstract

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.

Key words

Myocardial ischemia-reperfusion injury/Neutrophil/Ym-1/Cardiac immune response/Single-cell sequencing

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基金项目

National Natural Science Foundation of China(82022076)

National Natural Science Foundation of China(81974249)

National Natural Science Foundation of China(82070136)

National Natural Science Foundation of China(82104488)

National Natural Science Foundation of China(82305194)

Postdoctoral Science Foundation of China(2023M731222)

Postdoctoral Science Foundation of China(2020T130040ZX)

Foundation of Hubei Key Laboratory of Biological Targeted Therapy(2023swbx021)

出版年

2024

科学通报(英文版)

中国科学院

科学通报(英文版)

CSTPCD

ISSN：1001-6538

参考文献量43

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