{"title":"揭示败血症发病机制中 T 细胞亚群的动态变化和调控机制","authors":"Chunhui Jiang, Jiani Chen, Tong Sun, Jiaqin Xu, Hongguo Zhu, Jiaxi Chen","doi":"10.2147/ITT.S448691","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The pathogenesis of T cell subsets in sepsis during the body's resistance to infection is currently unknown. We aimed to investigate the dynamics and molecular mechanisms of T cells during the development of sepsis.</p><p><strong>Patients and methods: </strong>Perform single-cell data analysis on peripheral blood mononuclear cells (PBMCs) specimen samples from seven healthy controls, five early-stage sepsis patients, and four late sepsis patients, and the atlas were mapped and analyzed using reference mapping to identify the T cell subpopulations specific to early sepsis. Expression network upstream to investigate the changes of regulatory transcription factors and pathways by pySCENIC.</p><p><strong>Results: </strong>Twenty-two CD4<sup>+</sup> T-cell subpopulations and 10 CD8<sup>+</sup> T-cell subpopulations were identified by mapping analysis. At the early stage of sepsis, we observed altered ratios of multiple immune cells in PBMCs. Three cell types CD4 Tn cells, CD8 (GZMK<sup>+</sup> early Tem), and CD8 (ZNF683<sup>+</sup>CXCR6<sup>-</sup> Tm) showed an upward trend (p < 0.05) in the early stages of sepsis compared to normal and returned to normal levels after two weeks. In addition, we found the presence of four sepsis-specific transcription factors (MXI1, CHD1, ARID5A, KLF9) in these three types of cells, which were validated in two external datasets. The differentially expressed genes in CD4 Tn cells, CD8 (GZMK<sup>+</sup> early Tem), and CD8 (ZNF683<sup>+</sup>CXCR6<sup>-</sup> Tm) cells between the healthy group and the early-stage sepsis group are commonly enriched in the allograft rejection pathway. In addition, it was found that CD8 cells exhibit a trend towards differentiation into CD8 Temra cells in sepsis.</p><p><strong>Conclusion: </strong>We successfully depicted the dynamic changes of T cell subsets during sepsis onset and progression, which provides important clues for an in-depth understanding of T cells' function and regulatory mechanisms during sepsis pathogenesis.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"13 ","pages":"29-44"},"PeriodicalIF":6.2000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10844014/pdf/","citationCount":"0","resultStr":"{\"title\":\"Unveiling Dynamic Changes and Regulatory Mechanisms of T Cell Subsets in Sepsis Pathogenesis.\",\"authors\":\"Chunhui Jiang, Jiani Chen, Tong Sun, Jiaqin Xu, Hongguo Zhu, Jiaxi Chen\",\"doi\":\"10.2147/ITT.S448691\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>The pathogenesis of T cell subsets in sepsis during the body's resistance to infection is currently unknown. We aimed to investigate the dynamics and molecular mechanisms of T cells during the development of sepsis.</p><p><strong>Patients and methods: </strong>Perform single-cell data analysis on peripheral blood mononuclear cells (PBMCs) specimen samples from seven healthy controls, five early-stage sepsis patients, and four late sepsis patients, and the atlas were mapped and analyzed using reference mapping to identify the T cell subpopulations specific to early sepsis. Expression network upstream to investigate the changes of regulatory transcription factors and pathways by pySCENIC.</p><p><strong>Results: </strong>Twenty-two CD4<sup>+</sup> T-cell subpopulations and 10 CD8<sup>+</sup> T-cell subpopulations were identified by mapping analysis. At the early stage of sepsis, we observed altered ratios of multiple immune cells in PBMCs. Three cell types CD4 Tn cells, CD8 (GZMK<sup>+</sup> early Tem), and CD8 (ZNF683<sup>+</sup>CXCR6<sup>-</sup> Tm) showed an upward trend (p < 0.05) in the early stages of sepsis compared to normal and returned to normal levels after two weeks. In addition, we found the presence of four sepsis-specific transcription factors (MXI1, CHD1, ARID5A, KLF9) in these three types of cells, which were validated in two external datasets. The differentially expressed genes in CD4 Tn cells, CD8 (GZMK<sup>+</sup> early Tem), and CD8 (ZNF683<sup>+</sup>CXCR6<sup>-</sup> Tm) cells between the healthy group and the early-stage sepsis group are commonly enriched in the allograft rejection pathway. In addition, it was found that CD8 cells exhibit a trend towards differentiation into CD8 Temra cells in sepsis.</p><p><strong>Conclusion: </strong>We successfully depicted the dynamic changes of T cell subsets during sepsis onset and progression, which provides important clues for an in-depth understanding of T cells' function and regulatory mechanisms during sepsis pathogenesis.</p>\",\"PeriodicalId\":30986,\"journal\":{\"name\":\"ImmunoTargets and Therapy\",\"volume\":\"13 \",\"pages\":\"29-44\"},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2024-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10844014/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ImmunoTargets and Therapy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2147/ITT.S448691\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ImmunoTargets and Therapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/ITT.S448691","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的:目前尚不清楚机体抵抗感染过程中败血症中T细胞亚群的发病机制。我们旨在研究脓毒症发生过程中T细胞的动态变化和分子机制:对7名健康对照组、5名早期脓毒症患者和4名晚期脓毒症患者的外周血单核细胞(PBMCs)标本进行单细胞数据分析,并利用参考图谱对图谱进行映射和分析,以确定早期脓毒症特有的T细胞亚群。通过pySCENIC上游表达网络研究调控转录因子和通路的变化:结果:通过图谱分析确定了 22 个 CD4+ T 细胞亚群和 10 个 CD8+ T 细胞亚群。在败血症早期,我们观察到 PBMCs 中多种免疫细胞的比例发生了变化。三种细胞类型 CD4 Tn 细胞、CD8(GZMK+ early Tem)和 CD8(ZNF683+CXCR6- Tm)在脓毒症早期与正常相比呈上升趋势(p < 0.05),两周后恢复到正常水平。此外,我们还发现这三种细胞中存在四种败血症特异性转录因子(MXI1、CHD1、ARID5A、KLF9),这在两个外部数据集中得到了验证。健康组与早期脓毒症组之间的CD4 Tn细胞、CD8细胞(GZMK+ early Tem)和CD8细胞(ZNF683+CXCR6- Tm)中的差异表达基因通常富集在异体移植排斥途径中。此外,研究还发现脓毒症患者的 CD8 细胞有向 CD8 Temra 细胞分化的趋势:我们成功地描绘了脓毒症发病和发展过程中T细胞亚群的动态变化,为深入了解脓毒症发病过程中T细胞的功能和调控机制提供了重要线索。
Unveiling Dynamic Changes and Regulatory Mechanisms of T Cell Subsets in Sepsis Pathogenesis.
Purpose: The pathogenesis of T cell subsets in sepsis during the body's resistance to infection is currently unknown. We aimed to investigate the dynamics and molecular mechanisms of T cells during the development of sepsis.
Patients and methods: Perform single-cell data analysis on peripheral blood mononuclear cells (PBMCs) specimen samples from seven healthy controls, five early-stage sepsis patients, and four late sepsis patients, and the atlas were mapped and analyzed using reference mapping to identify the T cell subpopulations specific to early sepsis. Expression network upstream to investigate the changes of regulatory transcription factors and pathways by pySCENIC.
Results: Twenty-two CD4+ T-cell subpopulations and 10 CD8+ T-cell subpopulations were identified by mapping analysis. At the early stage of sepsis, we observed altered ratios of multiple immune cells in PBMCs. Three cell types CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6- Tm) showed an upward trend (p < 0.05) in the early stages of sepsis compared to normal and returned to normal levels after two weeks. In addition, we found the presence of four sepsis-specific transcription factors (MXI1, CHD1, ARID5A, KLF9) in these three types of cells, which were validated in two external datasets. The differentially expressed genes in CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6- Tm) cells between the healthy group and the early-stage sepsis group are commonly enriched in the allograft rejection pathway. In addition, it was found that CD8 cells exhibit a trend towards differentiation into CD8 Temra cells in sepsis.
Conclusion: We successfully depicted the dynamic changes of T cell subsets during sepsis onset and progression, which provides important clues for an in-depth understanding of T cells' function and regulatory mechanisms during sepsis pathogenesis.
期刊介绍:
Immuno Targets and Therapy is an international, peer-reviewed open access journal focusing on the immunological basis of diseases, potential targets for immune based therapy and treatment protocols employed to improve patient management. Basic immunology and physiology of the immune system in health, and disease will be also covered.In addition, the journal will focus on the impact of management programs and new therapeutic agents and protocols on patient perspectives such as quality of life, adherence and satisfaction.