{"title":"单细胞和大量 RNA 测序的整合揭示了类风湿关节炎患者的免疫异质性及其与疾病活动的关系。","authors":"Xiaofan Mao, Maohua Shi, Beiying Zhang, Rongdang Fu, Mengyun Cai, Sifei Yu, Kairong Lin, Chuling Zhang, Dingru Li, Guoqiang Chen, Wei Luo","doi":"10.1007/s12026-024-09513-5","DOIUrl":null,"url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease characterized by cartilage, bone damage, synovial inflammation, hyperplasia, autoantibody production, and systemic features. To obtain an overall profile of the immune environment in RA patients and its association with clinical features, we performed single-cell transcriptome and T-cell receptor sequencing of mononuclear cells from peripheral blood (PBMC) and synovial fluid (SF) from RA patients, integrated with two large cohorts with bulk RNA sequencing for further validation and investigation. Dendritic cells (DCs) exhibited relatively high functional heterogeneity and tissue specificity in relation to both antigen presentation and proinflammatory functions. Peripheral helper T cells (TPHs) are likely to originate from synovial tissue, undergo activation and exhaustion, and are subsequently released into the peripheral blood. Notably, among all immune cell types, TPHs were found to have the most intense associations with disease activity. In addition, CD8 effector T cells could be clustered into two groups with different cytokine expressions and play distinct roles in RA development. By integrating single-cell data with bulk sequencing from two large cohorts, we identified interactions among TPHs, CD8 cells, CD16 monocytes, and DCs that strongly contribute to the proinflammatory local environment in RA joints. Of note, the swollen 28-joint counts exhibited a more pronounced association with this immune environment compared to other disease activity indexes. The immune environment alternated significantly from PBMCs to SF, which indicated that a series of immune cells was involved in proinflammatory responses in the local joints of RA patients. By integrating single-cell data with two large cohorts, we have uncovered associations between specific immune cell populations and clinical features. This integration provides a rapid and precise methodology for assessing local immune activation, offering valuable insights into the pathophysiological mechanisms at play in RA.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1120-1135"},"PeriodicalIF":3.3000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Integration of single-cell and bulk RNA sequencing revealed immune heterogeneity and its association with disease activity in rheumatoid arthritis patients.\",\"authors\":\"Xiaofan Mao, Maohua Shi, Beiying Zhang, Rongdang Fu, Mengyun Cai, Sifei Yu, Kairong Lin, Chuling Zhang, Dingru Li, Guoqiang Chen, Wei Luo\",\"doi\":\"10.1007/s12026-024-09513-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease characterized by cartilage, bone damage, synovial inflammation, hyperplasia, autoantibody production, and systemic features. To obtain an overall profile of the immune environment in RA patients and its association with clinical features, we performed single-cell transcriptome and T-cell receptor sequencing of mononuclear cells from peripheral blood (PBMC) and synovial fluid (SF) from RA patients, integrated with two large cohorts with bulk RNA sequencing for further validation and investigation. Dendritic cells (DCs) exhibited relatively high functional heterogeneity and tissue specificity in relation to both antigen presentation and proinflammatory functions. Peripheral helper T cells (TPHs) are likely to originate from synovial tissue, undergo activation and exhaustion, and are subsequently released into the peripheral blood. Notably, among all immune cell types, TPHs were found to have the most intense associations with disease activity. In addition, CD8 effector T cells could be clustered into two groups with different cytokine expressions and play distinct roles in RA development. By integrating single-cell data with bulk sequencing from two large cohorts, we identified interactions among TPHs, CD8 cells, CD16 monocytes, and DCs that strongly contribute to the proinflammatory local environment in RA joints. Of note, the swollen 28-joint counts exhibited a more pronounced association with this immune environment compared to other disease activity indexes. The immune environment alternated significantly from PBMCs to SF, which indicated that a series of immune cells was involved in proinflammatory responses in the local joints of RA patients. By integrating single-cell data with two large cohorts, we have uncovered associations between specific immune cell populations and clinical features. This integration provides a rapid and precise methodology for assessing local immune activation, offering valuable insights into the pathophysiological mechanisms at play in RA.</p>\",\"PeriodicalId\":13389,\"journal\":{\"name\":\"Immunologic Research\",\"volume\":\" \",\"pages\":\"1120-1135\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunologic Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12026-024-09513-5\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunologic Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12026-024-09513-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/16 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
类风湿性关节炎(RA)是一种慢性、炎症性、全身性自身免疫性疾病,以软骨、骨损伤、滑膜炎症、增生、自身抗体产生和全身性特征为特征。为了全面了解 RA 患者的免疫环境及其与临床特征的关系,我们对 RA 患者外周血(PBMC)和滑膜液(SF)中的单核细胞进行了单细胞转录组和 T 细胞受体测序,并结合两个大型队列的批量 RNA 测序进行了进一步的验证和研究。树突状细胞(DC)在抗原呈递和促炎功能方面表现出较高的功能异质性和组织特异性。外周辅助 T 细胞(TPHs)可能来自滑膜组织,经过活化和衰竭,随后被释放到外周血中。值得注意的是,在所有免疫细胞类型中,TPHs 与疾病活动的关系最为密切。此外,CD8效应T细胞可分为细胞因子表达不同的两组,在RA发展过程中发挥着不同的作用。通过整合来自两个大型队列的单细胞数据和批量测序数据,我们发现了TPHs、CD8细胞、CD16单核细胞和DC之间的相互作用,这些相互作用对RA关节的局部促炎环境起着重要作用。值得注意的是,与其他疾病活动指数相比,28 个关节肿胀计数与这种免疫环境的关联更为明显。从PBMCs到SF,免疫环境明显交替变化,这表明一系列免疫细胞参与了RA患者局部关节的促炎反应。通过整合两个大型队列的单细胞数据,我们发现了特定免疫细胞群与临床特征之间的关联。这种整合为评估局部免疫激活提供了一种快速而精确的方法,为了解 RA 的病理生理机制提供了宝贵的见解。
Integration of single-cell and bulk RNA sequencing revealed immune heterogeneity and its association with disease activity in rheumatoid arthritis patients.
Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease characterized by cartilage, bone damage, synovial inflammation, hyperplasia, autoantibody production, and systemic features. To obtain an overall profile of the immune environment in RA patients and its association with clinical features, we performed single-cell transcriptome and T-cell receptor sequencing of mononuclear cells from peripheral blood (PBMC) and synovial fluid (SF) from RA patients, integrated with two large cohorts with bulk RNA sequencing for further validation and investigation. Dendritic cells (DCs) exhibited relatively high functional heterogeneity and tissue specificity in relation to both antigen presentation and proinflammatory functions. Peripheral helper T cells (TPHs) are likely to originate from synovial tissue, undergo activation and exhaustion, and are subsequently released into the peripheral blood. Notably, among all immune cell types, TPHs were found to have the most intense associations with disease activity. In addition, CD8 effector T cells could be clustered into two groups with different cytokine expressions and play distinct roles in RA development. By integrating single-cell data with bulk sequencing from two large cohorts, we identified interactions among TPHs, CD8 cells, CD16 monocytes, and DCs that strongly contribute to the proinflammatory local environment in RA joints. Of note, the swollen 28-joint counts exhibited a more pronounced association with this immune environment compared to other disease activity indexes. The immune environment alternated significantly from PBMCs to SF, which indicated that a series of immune cells was involved in proinflammatory responses in the local joints of RA patients. By integrating single-cell data with two large cohorts, we have uncovered associations between specific immune cell populations and clinical features. This integration provides a rapid and precise methodology for assessing local immune activation, offering valuable insights into the pathophysiological mechanisms at play in RA.
期刊介绍:
IMMUNOLOGIC RESEARCH represents a unique medium for the presentation, interpretation, and clarification of complex scientific data. Information is presented in the form of interpretive synthesis reviews, original research articles, symposia, editorials, and theoretical essays. The scope of coverage extends to cellular immunology, immunogenetics, molecular and structural immunology, immunoregulation and autoimmunity, immunopathology, tumor immunology, host defense and microbial immunity, including viral immunology, immunohematology, mucosal immunity, complement, transplantation immunology, clinical immunology, neuroimmunology, immunoendocrinology, immunotoxicology, translational immunology, and history of immunology.