{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:41:02Z","timestamp":1792172462922,"version":"4.4.0"},"reference-count":37,"publisher":"Wiley","issue":"34","license":[{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81930009"],"award-info":[{"award-number":["81930009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82230008"],"award-info":[{"award-number":["82230008"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870370"],"award-info":[{"award-number":["81870370"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070276"],"award-info":[{"award-number":["82070276"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800513"],"award-info":[{"award-number":["81800513"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["QC2018110"],"award-info":[{"award-number":["QC2018110"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The risk for suffering immune checkpoint inhibitors (ICIs)\u2010associated myocarditis increases in patients with pre\u2010existing conditions and the mechanisms remain to be clarified. Spatial transcriptomics, single\u2010cell RNA sequencing, and flow cytometry are used to decipher how anti\u2010cytotoxic T lymphocyte antigen\u20104 m2a antibody (anti\u2010CTLA\u20104 m2a antibody) aggravated cardiac injury in experimental autoimmune myocarditis (EAM) mice. It is found that anti\u2010CTLA\u20104 m2a antibody increases cardiac fibroblast\u2010derived C\u2010X\u2010C motif chemokine ligand 1 (Cxcl1), which promots neutrophil infiltration to the myocarditic zones (MZs) of EAM mice via enhanced Cxcl1\u2010Cxcr2 chemotaxis. It is identified that the C\u2013C motif chemokine ligand 5 (Ccl5)\u2010neutrophil subpopulation is responsible for high activity of cytokine production, adaptive immune response, NF\u2010\u03baB signaling, and cellular response to interferon\u2010gamma and that the Ccl5\u2010neutrophil subpopulation and its\u2010associated proinflammatory cytokines\/chemokines promoted macrophage (M\u03c6) polarization to M1 M\u03c6. These altered infiltrating landscape and phenotypic switch of immune cells, and proinflammatory factors synergistically aggravated anti\u2010CTLA\u20104 m2a antibody\u2010induced cardiac injury in EAM mice. Neutralizing neutrophils, Cxcl1, and applying Cxcr2 antagonist dramatically alleviates anti\u2010CTLA\u20104 m2a antibody\u2010induced leukocyte infiltration, cardiac fibrosis, and dysfunction. It is suggested that Ccl5\u2010neutrophil subpopulation plays a critical role in aggravating anti\u2010CTLA\u20104 m2a antibody\u2010induced cardiac injury in EAM mice. This data may provide a strategic rational for preventing\/curing ICIs\u2010associated myocarditis.<\/jats:p>","DOI":"10.1002\/advs.202400486","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T01:42:27Z","timestamp":1720489347000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Anti\u2010CTLA\u20104 m2a Antibody Exacerbates Cardiac Injury in Experimental Autoimmune Myocarditis Mice By Promoting Ccl5\u2010Neutrophil Infiltration"],"prefix":"10.1002","volume":"11","author":[{"given":"Ming\u2010Ming","family":"Wu","sequence":"first","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine The First Affiliated Hospital of Harbin Medical University (HMU) NHC Key Laboratory of Cell Transplantation Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment  Harbin 150001 China"},{"name":"Departments of Cardiology and Pharmacy HMU Cancer Hospital Insitute of Metabolic Disease Heilongjiang Academy of Medical Science Heilongjiang key laboratory for Metabolic disorder and cancer related cardiovascular diseases  Harbin 150081 China"},{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) HMU  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Chao","family":"Yang","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine The First Affiliated Hospital of Harbin Medical University (HMU) NHC Key Laboratory of Cell Transplantation Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment  Harbin 150001 China"},{"name":"Departments of Cardiology and Pharmacy HMU Cancer Hospital Insitute of Metabolic Disease Heilongjiang Academy of Medical Science Heilongjiang key laboratory for Metabolic disorder and cancer related cardiovascular diseases  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Xu","family":"Cai","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Pharmacy HMU Cancer Hospital Insitute of Metabolic Disease Heilongjiang Academy of Medical Science Heilongjiang key laboratory for Metabolic disorder and cancer related cardiovascular diseases  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Jiang","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Pharmacy HMU Cancer Hospital Insitute of Metabolic Disease Heilongjiang Academy of Medical Science Heilongjiang key laboratory for Metabolic disorder and cancer related cardiovascular diseases  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Xiao","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine The First Affiliated Hospital of Harbin Medical University (HMU) NHC Key Laboratory of Cell Transplantation Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment  Harbin 150001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Miao","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine The First Affiliated Hospital of Harbin Medical University (HMU) NHC Key Laboratory of Cell Transplantation Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment  Harbin 150001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi\u2010Yun","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Interdisciplinary Medicine and Engineering HMU  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine The First Affiliated Hospital of Harbin Medical University (HMU) NHC Key Laboratory of Cell Transplantation Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment  Harbin 150001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Bi","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine The First Affiliated Hospital of Harbin Medical University (HMU) NHC Key Laboratory of Cell Transplantation Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment  Harbin 150001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi","family":"Hong","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine The First Affiliated Hospital of Harbin Medical University (HMU) NHC Key Laboratory of Cell Transplantation Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment  Harbin 150001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhu","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine The First Affiliated Hospital of Harbin Medical University (HMU) NHC Key Laboratory of Cell Transplantation Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment  Harbin 150001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Yu","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine The First Affiliated Hospital of Harbin Medical University (HMU) NHC Key Laboratory of Cell Transplantation Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment  Harbin 150001 China"},{"name":"Departments of Cardiology and Pharmacy HMU Cancer Hospital Insitute of Metabolic Disease Heilongjiang Academy of Medical Science Heilongjiang key laboratory for Metabolic disorder and cancer related cardiovascular diseases  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Jun","family":"Mao","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine The First Affiliated Hospital of Harbin Medical University (HMU) NHC Key Laboratory of Cell Transplantation Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment  Harbin 150001 China"},{"name":"Departments of Cardiology and Pharmacy HMU Cancer Hospital Insitute of Metabolic Disease Heilongjiang Academy of Medical Science Heilongjiang key laboratory for Metabolic disorder and cancer related cardiovascular diseases  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang\u2010Jiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Pharmacy HMU Cancer Hospital Insitute of Metabolic Disease Heilongjiang Academy of Medical Science Heilongjiang key laboratory for Metabolic disorder and cancer related cardiovascular diseases  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liang","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine The First Affiliated Hospital of Harbin Medical University (HMU) NHC Key Laboratory of Cell Transplantation Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment  Harbin 150001 China"},{"name":"Departments of Cardiology and Pharmacy HMU Cancer Hospital Insitute of Metabolic Disease Heilongjiang Academy of Medical Science Heilongjiang key laboratory for Metabolic disorder and cancer related cardiovascular diseases  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang\u2010Liang","family":"Tang","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Pharmacy HMU Cancer Hospital Insitute of Metabolic Disease Heilongjiang Academy of Medical Science Heilongjiang key laboratory for Metabolic disorder and cancer related cardiovascular diseases  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu\u2010Shi","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine The First Affiliated Hospital of Harbin Medical University (HMU) NHC Key Laboratory of Cell Transplantation Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment  Harbin 150001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Shao","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Pharmacy HMU Cancer Hospital Insitute of Metabolic Disease Heilongjiang Academy of Medical Science Heilongjiang key laboratory for Metabolic disorder and cancer related cardiovascular diseases  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing\u2010Hua","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Interdisciplinary Medicine and Engineering HMU  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen\u2010Wei","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) HMU  Harbin 150081 China"},{"name":"Department of Pharmacology (State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China) Key Laboratory of Cardiovascular Medicine Research Ministry of Education) HMU  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1324-6934","authenticated-orcid":false,"given":"Zhi\u2010Ren","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Cardiology and Critical Care Medicine The First Affiliated Hospital of Harbin Medical University (HMU) NHC Key Laboratory of Cell Transplantation Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment  Harbin 150001 China"},{"name":"Departments of Cardiology and Pharmacy HMU Cancer Hospital Insitute of Metabolic Disease Heilongjiang Academy of Medical Science Heilongjiang key laboratory for Metabolic disorder and cancer related cardiovascular diseases  Harbin 150081 China"},{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD) HMU  Harbin 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.02.037"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.3113"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2020.02.016"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccao.2022.11.008"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609214"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1603892113"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-4083"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-0856"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916930802031579"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05432-3"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118642"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(10)80331-6"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63169-0"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.1026866"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvac052"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0224377"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","unstructured":"N.Lasrado N.Borcherding R.Arumugam T. K.Starr J.Reddy iScience2022 25 103865 .","DOI":"10.1016\/j.isci.2022.103865"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43882"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113174"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.043545"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1812186116"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0762"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.05.027"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-11-125435"},{"key":"e_1_2_9_20_3","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-022-00447-1"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00832-3"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00157"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx017"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.038820"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200389"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.2741\/s33"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy085"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.020754"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu062"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.05.004"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.062551"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-022-00138-1"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202400486","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T13:13:04Z","timestamp":1759756384000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202400486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,8]]},"references-count":37,"journal-issue":{"issue":"34","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/advs.202400486"],"URL":"https:\/\/doi.org\/10.1002\/advs.202400486","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,8]]},"assertion":[{"value":"2024-01-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2400486"}}