Jianpei Wen, Huihui Li, Yufei Zhou, Hengzhi Du, Guo Hu, Zheng Wen, Du Tang, Yanwen Wang, Xinwu Cui, Zhou Zhou, Dao Wen Wang, Chen Chen
{"title":"免疫球蛋白通过抑制过度激活的先天性免疫反应减轻暴发性心肌炎的病情","authors":"Jianpei Wen, Huihui Li, Yufei Zhou, Hengzhi Du, Guo Hu, Zheng Wen, Du Tang, Yanwen Wang, Xinwu Cui, Zhou Zhou, Dao Wen Wang, Chen Chen","doi":"10.1111/bph.17372","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and purpose: </strong>Fulminant myocarditis (FM) is a myocardial inflammatory disease that can result from either viral diseases or autoimmune diseases. In this study, we have determined the treatment effects of immunomodulatory drugs on FM.</p><p><strong>Experimental approach: </strong>FM was induced in A/JGpt mice by intraperitoneal administration of coxsackievirus B3, after which immunoglobins were administered daily by intraperitoneal injection. On the seventh day, the cardiac structure and function were determined using echocardiography and cardiac catheterisation. Single-cell RNA sequencing (scRNA-seq) was performed to evaluate CD45<sup>+</sup> cells in the heart.</p><p><strong>Key results: </strong>Immunoglobin, a typical immunomodulatory drug, dramatically reduced mortality and significantly improved cardiac function in mice with FM. ScRNA-seq revealed that immunoglobin treatment effectively modulated cardiac immune homeostasis, particularly by attenuating overactivated innate immune responses. At the cellular level, immunoglobin predominantly targeted Plac8<sup>+</sup> monocytes and S100a8<sup>+</sup> neutrophils, suppressing their proinflammatory activities, and enhancing antigen processing and presentation capabilities, thereby amplifying the efficiency and potency of the immune response against the virus. Immunoglobin benefits are mediated by the modulation of multiple signalling pathways, including relevant receptors on immune cells, direction of inflammatory cell chemotaxis, antigen presentation and anti-viral effects. Subsequently, Bst2-ILT7 ligand-receptor-mediated cellular interactions manipulated by immunoglobin were further confirmed in vivo.</p><p><strong>Conclusions and implications: </strong>Immunoglobin treatment significantly attenuated FM-induced cardiac inflammation and improved cardiac function by inhibiting overactivated innate immune responses.</p>","PeriodicalId":9262,"journal":{"name":"British Journal of Pharmacology","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Immunoglobin attenuates fulminant myocarditis by inhibiting overactivated innate immune response.\",\"authors\":\"Jianpei Wen, Huihui Li, Yufei Zhou, Hengzhi Du, Guo Hu, Zheng Wen, Du Tang, Yanwen Wang, Xinwu Cui, Zhou Zhou, Dao Wen Wang, Chen Chen\",\"doi\":\"10.1111/bph.17372\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and purpose: </strong>Fulminant myocarditis (FM) is a myocardial inflammatory disease that can result from either viral diseases or autoimmune diseases. In this study, we have determined the treatment effects of immunomodulatory drugs on FM.</p><p><strong>Experimental approach: </strong>FM was induced in A/JGpt mice by intraperitoneal administration of coxsackievirus B3, after which immunoglobins were administered daily by intraperitoneal injection. On the seventh day, the cardiac structure and function were determined using echocardiography and cardiac catheterisation. Single-cell RNA sequencing (scRNA-seq) was performed to evaluate CD45<sup>+</sup> cells in the heart.</p><p><strong>Key results: </strong>Immunoglobin, a typical immunomodulatory drug, dramatically reduced mortality and significantly improved cardiac function in mice with FM. ScRNA-seq revealed that immunoglobin treatment effectively modulated cardiac immune homeostasis, particularly by attenuating overactivated innate immune responses. At the cellular level, immunoglobin predominantly targeted Plac8<sup>+</sup> monocytes and S100a8<sup>+</sup> neutrophils, suppressing their proinflammatory activities, and enhancing antigen processing and presentation capabilities, thereby amplifying the efficiency and potency of the immune response against the virus. Immunoglobin benefits are mediated by the modulation of multiple signalling pathways, including relevant receptors on immune cells, direction of inflammatory cell chemotaxis, antigen presentation and anti-viral effects. Subsequently, Bst2-ILT7 ligand-receptor-mediated cellular interactions manipulated by immunoglobin were further confirmed in vivo.</p><p><strong>Conclusions and implications: </strong>Immunoglobin treatment significantly attenuated FM-induced cardiac inflammation and improved cardiac function by inhibiting overactivated innate immune responses.</p>\",\"PeriodicalId\":9262,\"journal\":{\"name\":\"British Journal of Pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2024-10-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"British Journal of Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/bph.17372\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"British Journal of Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/bph.17372","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Immunoglobin attenuates fulminant myocarditis by inhibiting overactivated innate immune response.
Background and purpose: Fulminant myocarditis (FM) is a myocardial inflammatory disease that can result from either viral diseases or autoimmune diseases. In this study, we have determined the treatment effects of immunomodulatory drugs on FM.
Experimental approach: FM was induced in A/JGpt mice by intraperitoneal administration of coxsackievirus B3, after which immunoglobins were administered daily by intraperitoneal injection. On the seventh day, the cardiac structure and function were determined using echocardiography and cardiac catheterisation. Single-cell RNA sequencing (scRNA-seq) was performed to evaluate CD45+ cells in the heart.
Key results: Immunoglobin, a typical immunomodulatory drug, dramatically reduced mortality and significantly improved cardiac function in mice with FM. ScRNA-seq revealed that immunoglobin treatment effectively modulated cardiac immune homeostasis, particularly by attenuating overactivated innate immune responses. At the cellular level, immunoglobin predominantly targeted Plac8+ monocytes and S100a8+ neutrophils, suppressing their proinflammatory activities, and enhancing antigen processing and presentation capabilities, thereby amplifying the efficiency and potency of the immune response against the virus. Immunoglobin benefits are mediated by the modulation of multiple signalling pathways, including relevant receptors on immune cells, direction of inflammatory cell chemotaxis, antigen presentation and anti-viral effects. Subsequently, Bst2-ILT7 ligand-receptor-mediated cellular interactions manipulated by immunoglobin were further confirmed in vivo.
Conclusions and implications: Immunoglobin treatment significantly attenuated FM-induced cardiac inflammation and improved cardiac function by inhibiting overactivated innate immune responses.
期刊介绍:
The British Journal of Pharmacology (BJP) is a biomedical science journal offering comprehensive international coverage of experimental and translational pharmacology. It publishes original research, authoritative reviews, mini reviews, systematic reviews, meta-analyses, databases, letters to the Editor, and commentaries.
Review articles, databases, systematic reviews, and meta-analyses are typically commissioned, but unsolicited contributions are also considered, either as standalone papers or part of themed issues.
In addition to basic science research, BJP features translational pharmacology research, including proof-of-concept and early mechanistic studies in humans. While it generally does not publish first-in-man phase I studies or phase IIb, III, or IV studies, exceptions may be made under certain circumstances, particularly if results are combined with preclinical studies.