{"title":"通过 CyTOF 发现 Ly6ChiCD103+ 髓系细胞与辐射诱导的心脏纤维化之间的联系","authors":"","doi":"10.1016/j.jrras.2024.101042","DOIUrl":null,"url":null,"abstract":"<div><p>Several immune cell populations participate in the development of radiation-induced cardiac fibrosis. However, the underlying mechanism remains to be elucidated. Male C57BL/6 mice (8–12 weeks old) were anesthetized and exposed to a single cardiac radiation dose of 20 Gy using the small-animal radiation research platform. We conducted echocardiography and histological analysis to identify cardiac fibrosis from a functional and pathological perspective. Time-of-flight mass cytometry (CyTOF) was used to describe the compositional changes of immune cells 1, 4, and 8 weeks after cardiac irradiation in mouse peripheral blood and cardiac tissue samples. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure CD14 and CD105 mRNA levels from peripheral blood cells in eight patients who received thoracic radiotherapy 6 months ago. We observed reduced cardiac systolic function and increased collagen deposition in cardiac tissue after irradiation. Transforming growth factor-β, tumor necrosis factor-α, and interleukin-6 expression significantly elevated in the plasma. We identified a significant increase in CD45<sup>+</sup> immune cell levels four weeks after cardiac irradiation using CyTOF, and neutrophil, monocyte, and macrophage levels elevated in blood samples after cardiac irradiation (four weeks). In cardiac tissue samples, monocyte and macrophage levels increased after cardiac irradiation (four weeks) compared with control group. Macrophages and monocytes were further analyzed, and the proportion of Ly6C<sup>hi</sup>CD103<sup>+</sup> myeloid cells increased after cardiac irradiation in tissue samples (four weeks). RT-qPCR revealed that CD14 expression was higher in patients with cardiac injured group than in the control group (Previous studies reported that Ly6C<sup>hi</sup> monocytes in mice are similar to CD14 + CD16<sup>−</sup> monocytes in humans). We found that Ly6C<sup>hi</sup>CD103<sup>+</sup> myeloid cells are critical subsets in radiation-induced cardiac fibrosis and might play protective roles in the process. Ly6C<sup>hi</sup>CD103<sup>+</sup> myeloid cells may be considered an early biomarker for detecting radiation-induced cardiac fibrosis.</p></div>","PeriodicalId":16920,"journal":{"name":"Journal of Radiation Research and Applied Sciences","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1687850724002267/pdfft?md5=b7c1a743ec82b2945104b1c1239b666a&pid=1-s2.0-S1687850724002267-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Uncovering the connection between Ly6ChiCD103+ myeloid cells and radiation-induced cardiac fibrosis by CyTOF\",\"authors\":\"\",\"doi\":\"10.1016/j.jrras.2024.101042\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Several immune cell populations participate in the development of radiation-induced cardiac fibrosis. However, the underlying mechanism remains to be elucidated. Male C57BL/6 mice (8–12 weeks old) were anesthetized and exposed to a single cardiac radiation dose of 20 Gy using the small-animal radiation research platform. We conducted echocardiography and histological analysis to identify cardiac fibrosis from a functional and pathological perspective. Time-of-flight mass cytometry (CyTOF) was used to describe the compositional changes of immune cells 1, 4, and 8 weeks after cardiac irradiation in mouse peripheral blood and cardiac tissue samples. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure CD14 and CD105 mRNA levels from peripheral blood cells in eight patients who received thoracic radiotherapy 6 months ago. We observed reduced cardiac systolic function and increased collagen deposition in cardiac tissue after irradiation. Transforming growth factor-β, tumor necrosis factor-α, and interleukin-6 expression significantly elevated in the plasma. We identified a significant increase in CD45<sup>+</sup> immune cell levels four weeks after cardiac irradiation using CyTOF, and neutrophil, monocyte, and macrophage levels elevated in blood samples after cardiac irradiation (four weeks). In cardiac tissue samples, monocyte and macrophage levels increased after cardiac irradiation (four weeks) compared with control group. Macrophages and monocytes were further analyzed, and the proportion of Ly6C<sup>hi</sup>CD103<sup>+</sup> myeloid cells increased after cardiac irradiation in tissue samples (four weeks). RT-qPCR revealed that CD14 expression was higher in patients with cardiac injured group than in the control group (Previous studies reported that Ly6C<sup>hi</sup> monocytes in mice are similar to CD14 + CD16<sup>−</sup> monocytes in humans). We found that Ly6C<sup>hi</sup>CD103<sup>+</sup> myeloid cells are critical subsets in radiation-induced cardiac fibrosis and might play protective roles in the process. Ly6C<sup>hi</sup>CD103<sup>+</sup> myeloid cells may be considered an early biomarker for detecting radiation-induced cardiac fibrosis.</p></div>\",\"PeriodicalId\":16920,\"journal\":{\"name\":\"Journal of Radiation Research and Applied Sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-07-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1687850724002267/pdfft?md5=b7c1a743ec82b2945104b1c1239b666a&pid=1-s2.0-S1687850724002267-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Radiation Research and Applied Sciences\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1687850724002267\",\"RegionNum\":4,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Radiation Research and Applied Sciences","FirstCategoryId":"103","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1687850724002267","RegionNum":4,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Uncovering the connection between Ly6ChiCD103+ myeloid cells and radiation-induced cardiac fibrosis by CyTOF
Several immune cell populations participate in the development of radiation-induced cardiac fibrosis. However, the underlying mechanism remains to be elucidated. Male C57BL/6 mice (8–12 weeks old) were anesthetized and exposed to a single cardiac radiation dose of 20 Gy using the small-animal radiation research platform. We conducted echocardiography and histological analysis to identify cardiac fibrosis from a functional and pathological perspective. Time-of-flight mass cytometry (CyTOF) was used to describe the compositional changes of immune cells 1, 4, and 8 weeks after cardiac irradiation in mouse peripheral blood and cardiac tissue samples. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure CD14 and CD105 mRNA levels from peripheral blood cells in eight patients who received thoracic radiotherapy 6 months ago. We observed reduced cardiac systolic function and increased collagen deposition in cardiac tissue after irradiation. Transforming growth factor-β, tumor necrosis factor-α, and interleukin-6 expression significantly elevated in the plasma. We identified a significant increase in CD45+ immune cell levels four weeks after cardiac irradiation using CyTOF, and neutrophil, monocyte, and macrophage levels elevated in blood samples after cardiac irradiation (four weeks). In cardiac tissue samples, monocyte and macrophage levels increased after cardiac irradiation (four weeks) compared with control group. Macrophages and monocytes were further analyzed, and the proportion of Ly6ChiCD103+ myeloid cells increased after cardiac irradiation in tissue samples (four weeks). RT-qPCR revealed that CD14 expression was higher in patients with cardiac injured group than in the control group (Previous studies reported that Ly6Chi monocytes in mice are similar to CD14 + CD16− monocytes in humans). We found that Ly6ChiCD103+ myeloid cells are critical subsets in radiation-induced cardiac fibrosis and might play protective roles in the process. Ly6ChiCD103+ myeloid cells may be considered an early biomarker for detecting radiation-induced cardiac fibrosis.
期刊介绍:
Journal of Radiation Research and Applied Sciences provides a high quality medium for the publication of substantial, original and scientific and technological papers on the development and applications of nuclear, radiation and isotopes in biology, medicine, drugs, biochemistry, microbiology, agriculture, entomology, food technology, chemistry, physics, solid states, engineering, environmental and applied sciences.