{"title":"脓毒症后持续炎症、免疫抑制和分解代谢综合征的免疫细胞特征。","authors":"Xing-Feng Sun, Wen-Chen Luo, Shao-Qiang Huang, Yi-Jun Zheng, Lei Xiao, Zhong-Wei Zhang, Rong-Hua Liu, Zi-Wen Zhong, Jie-Qiong Song, Ke Nan, Zhi-Xin Qiu, Jing Zhong, Chang-Hong Miao","doi":"10.1016/j.medj.2024.12.003","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Management of persistent inflammation, immunosuppression, and catabolism syndrome (PICS) after sepsis remains challenging for patients in the intensive care unit, experiencing poor quality of life and death. However, immune-cell signatures in patients with PICS after sepsis remain unclear.</p><p><strong>Methods: </strong>We determined immune-cell signatures of PICS after sepsis at single-cell resolution. Murine cecal ligation and puncture models of PICS were applied for validation.</p><p><strong>Findings: </strong>Immune functions of two enriched monocyte subpopulations, Mono1 and Mono4, were suppressed substantially in patients with sepsis and were partially restored in patients with PICS after sepsis and exhibited immunosuppressive and pro-apoptotic effects on B and CD8T cells. Patients with PICS and sepsis had reduced naive and memory B cells and proliferated plasma cells. Besides, naive and memory B cells in patients with PICS showed an active antigen processing and presentation gene signature compared to those with sepsis. PICS patients with better prognoses exhibited more active memory B cells and IGHA1-plasma cells. CD8TEMRA displayed signs of proliferation and immune dysfunction in the PICS-death group in contrast with the PICS-alive group. Megakaryocytes proliferation was more pronounced in patients with PICS and sepsis than in healthy controls, with notable changes in the anti-inflammatory and immunomodulatory effects observed in patients with PICS and verified in mice models.</p><p><strong>Conclusions: </strong>Our study evaluated PICS after sepsis at the single-cell level, identifying the heterogeneity present within immune-cell subsets, facilitating the prediction of disease progression and the development of effective intervention.</p><p><strong>Funding: </strong>This work was supported by the National Natural Science Foundation of China, Shanghai Municipal Health Commission \"Yiyuan New Star\" Youth Medical Talent Cultivating Program, and Shanghai Clinical Research Center for Anesthesiology.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":""},"PeriodicalIF":12.8000,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Immune-cell signatures of persistent inflammation, immunosuppression, and catabolism syndrome after sepsis.\",\"authors\":\"Xing-Feng Sun, Wen-Chen Luo, Shao-Qiang Huang, Yi-Jun Zheng, Lei Xiao, Zhong-Wei Zhang, Rong-Hua Liu, Zi-Wen Zhong, Jie-Qiong Song, Ke Nan, Zhi-Xin Qiu, Jing Zhong, Chang-Hong Miao\",\"doi\":\"10.1016/j.medj.2024.12.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Management of persistent inflammation, immunosuppression, and catabolism syndrome (PICS) after sepsis remains challenging for patients in the intensive care unit, experiencing poor quality of life and death. However, immune-cell signatures in patients with PICS after sepsis remain unclear.</p><p><strong>Methods: </strong>We determined immune-cell signatures of PICS after sepsis at single-cell resolution. Murine cecal ligation and puncture models of PICS were applied for validation.</p><p><strong>Findings: </strong>Immune functions of two enriched monocyte subpopulations, Mono1 and Mono4, were suppressed substantially in patients with sepsis and were partially restored in patients with PICS after sepsis and exhibited immunosuppressive and pro-apoptotic effects on B and CD8T cells. Patients with PICS and sepsis had reduced naive and memory B cells and proliferated plasma cells. Besides, naive and memory B cells in patients with PICS showed an active antigen processing and presentation gene signature compared to those with sepsis. PICS patients with better prognoses exhibited more active memory B cells and IGHA1-plasma cells. CD8TEMRA displayed signs of proliferation and immune dysfunction in the PICS-death group in contrast with the PICS-alive group. Megakaryocytes proliferation was more pronounced in patients with PICS and sepsis than in healthy controls, with notable changes in the anti-inflammatory and immunomodulatory effects observed in patients with PICS and verified in mice models.</p><p><strong>Conclusions: </strong>Our study evaluated PICS after sepsis at the single-cell level, identifying the heterogeneity present within immune-cell subsets, facilitating the prediction of disease progression and the development of effective intervention.</p><p><strong>Funding: </strong>This work was supported by the National Natural Science Foundation of China, Shanghai Municipal Health Commission \\\"Yiyuan New Star\\\" Youth Medical Talent Cultivating Program, and Shanghai Clinical Research Center for Anesthesiology.</p>\",\"PeriodicalId\":29964,\"journal\":{\"name\":\"Med\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":12.8000,\"publicationDate\":\"2025-01-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Med\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.medj.2024.12.003\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Med","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.medj.2024.12.003","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Immune-cell signatures of persistent inflammation, immunosuppression, and catabolism syndrome after sepsis.
Background: Management of persistent inflammation, immunosuppression, and catabolism syndrome (PICS) after sepsis remains challenging for patients in the intensive care unit, experiencing poor quality of life and death. However, immune-cell signatures in patients with PICS after sepsis remain unclear.
Methods: We determined immune-cell signatures of PICS after sepsis at single-cell resolution. Murine cecal ligation and puncture models of PICS were applied for validation.
Findings: Immune functions of two enriched monocyte subpopulations, Mono1 and Mono4, were suppressed substantially in patients with sepsis and were partially restored in patients with PICS after sepsis and exhibited immunosuppressive and pro-apoptotic effects on B and CD8T cells. Patients with PICS and sepsis had reduced naive and memory B cells and proliferated plasma cells. Besides, naive and memory B cells in patients with PICS showed an active antigen processing and presentation gene signature compared to those with sepsis. PICS patients with better prognoses exhibited more active memory B cells and IGHA1-plasma cells. CD8TEMRA displayed signs of proliferation and immune dysfunction in the PICS-death group in contrast with the PICS-alive group. Megakaryocytes proliferation was more pronounced in patients with PICS and sepsis than in healthy controls, with notable changes in the anti-inflammatory and immunomodulatory effects observed in patients with PICS and verified in mice models.
Conclusions: Our study evaluated PICS after sepsis at the single-cell level, identifying the heterogeneity present within immune-cell subsets, facilitating the prediction of disease progression and the development of effective intervention.
Funding: This work was supported by the National Natural Science Foundation of China, Shanghai Municipal Health Commission "Yiyuan New Star" Youth Medical Talent Cultivating Program, and Shanghai Clinical Research Center for Anesthesiology.
期刊介绍：
Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically.
Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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