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TREM2(hi) resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis
Sepsis-induced cardiomyopathy (SICM) is common in septic patients with a high mortality and is characterized by an abnormal immune response. Owing to cellular heterogeneity, understanding the roles of immune cell subsets in SICM has been challenging. Here we identify a unique subpopulation of cardia...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886554/ https://www.ncbi.nlm.nih.gov/pubmed/36635449 http://dx.doi.org/10.1038/s42255-022-00715-5 |
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author | Zhang, Kai Wang, Yang Chen, Shiyu Mao, Jiali Jin, Yue Ye, Hui Zhang, Yan Liu, Xiwang Gong, Chenchen Cheng, Xuejun Huang, Xiaoli Hoeft, Andreas Chen, Qixing Li, Xuekun Fang, Xiangming |
author_facet | Zhang, Kai Wang, Yang Chen, Shiyu Mao, Jiali Jin, Yue Ye, Hui Zhang, Yan Liu, Xiwang Gong, Chenchen Cheng, Xuejun Huang, Xiaoli Hoeft, Andreas Chen, Qixing Li, Xuekun Fang, Xiangming |
author_sort | Zhang, Kai |
collection | PubMed |
description | Sepsis-induced cardiomyopathy (SICM) is common in septic patients with a high mortality and is characterized by an abnormal immune response. Owing to cellular heterogeneity, understanding the roles of immune cell subsets in SICM has been challenging. Here we identify a unique subpopulation of cardiac-resident macrophages termed CD163(+)RETNLA(+) (Mac1), which undergoes self-renewal during sepsis and can be targeted to prevent SICM. By combining single-cell RNA sequencing with fate mapping in a mouse model of sepsis, we demonstrate that the Mac1 subpopulation has distinct transcriptomic signatures enriched in endocytosis and displays high expression of TREM2 (TREM2(hi)). TREM2(hi) Mac1 cells actively scavenge cardiomyocyte-ejected dysfunctional mitochondria. Trem2 deficiency in macrophages impairs the self-renewal capability of the Mac1 subpopulation and consequently results in defective elimination of damaged mitochondria, excessive inflammatory response in cardiac tissue, exacerbated cardiac dysfunction and decreased survival. Notably, intrapericardial administration of TREM2(hi) Mac1 cells prevents SICM. Our findings suggest that the modulation of TREM2(hi) Mac1 cells could serve as a therapeutic strategy for SICM. |
format | Online Article Text |
id | pubmed-9886554 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98865542023-02-01 TREM2(hi) resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis Zhang, Kai Wang, Yang Chen, Shiyu Mao, Jiali Jin, Yue Ye, Hui Zhang, Yan Liu, Xiwang Gong, Chenchen Cheng, Xuejun Huang, Xiaoli Hoeft, Andreas Chen, Qixing Li, Xuekun Fang, Xiangming Nat Metab Article Sepsis-induced cardiomyopathy (SICM) is common in septic patients with a high mortality and is characterized by an abnormal immune response. Owing to cellular heterogeneity, understanding the roles of immune cell subsets in SICM has been challenging. Here we identify a unique subpopulation of cardiac-resident macrophages termed CD163(+)RETNLA(+) (Mac1), which undergoes self-renewal during sepsis and can be targeted to prevent SICM. By combining single-cell RNA sequencing with fate mapping in a mouse model of sepsis, we demonstrate that the Mac1 subpopulation has distinct transcriptomic signatures enriched in endocytosis and displays high expression of TREM2 (TREM2(hi)). TREM2(hi) Mac1 cells actively scavenge cardiomyocyte-ejected dysfunctional mitochondria. Trem2 deficiency in macrophages impairs the self-renewal capability of the Mac1 subpopulation and consequently results in defective elimination of damaged mitochondria, excessive inflammatory response in cardiac tissue, exacerbated cardiac dysfunction and decreased survival. Notably, intrapericardial administration of TREM2(hi) Mac1 cells prevents SICM. Our findings suggest that the modulation of TREM2(hi) Mac1 cells could serve as a therapeutic strategy for SICM. Nature Publishing Group UK 2023-01-12 2023 /pmc/articles/PMC9886554/ /pubmed/36635449 http://dx.doi.org/10.1038/s42255-022-00715-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zhang, Kai Wang, Yang Chen, Shiyu Mao, Jiali Jin, Yue Ye, Hui Zhang, Yan Liu, Xiwang Gong, Chenchen Cheng, Xuejun Huang, Xiaoli Hoeft, Andreas Chen, Qixing Li, Xuekun Fang, Xiangming TREM2(hi) resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis |
title | TREM2(hi) resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis |
title_full | TREM2(hi) resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis |
title_fullStr | TREM2(hi) resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis |
title_full_unstemmed | TREM2(hi) resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis |
title_short | TREM2(hi) resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis |
title_sort | trem2(hi) resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886554/ https://www.ncbi.nlm.nih.gov/pubmed/36635449 http://dx.doi.org/10.1038/s42255-022-00715-5 |
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