Institute of Translational Medicine, The First People's Hospital of Foshan, Foshan, China.
Department of Rheumatology, The First People's Hospital of Foshan, Foshan, China.
Immunol Res. 2024 Oct;72(5):1120-1135. doi: 10.1007/s12026-024-09513-5. Epub 2024 Jul 16.
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.
类风湿关节炎（RA）是一种慢性、炎症性、系统性自身免疫性疾病，其特征为软骨、骨损伤、滑膜炎症、增生、自身抗体产生和全身表现。为了全面了解 RA 患者的免疫环境及其与临床特征的关联，我们对 RA 患者外周血（PBMC）和滑膜液（SF）的单核细胞进行了单细胞转录组和 T 细胞受体测序，并与两个大型 RNA 测序队列进行了整合，以进一步验证和研究。树突状细胞（DC）在抗原呈递和促炎功能方面表现出相对较高的功能异质性和组织特异性。外周辅助性 T 细胞（TPH）可能来源于滑膜组织，经历激活和衰竭，随后释放到外周血中。值得注意的是，在所有免疫细胞类型中，TPH 与疾病活动度的关联最为密切。此外，CD8 效应 T 细胞可以聚类为具有不同细胞因子表达的两组，在 RA 发展中发挥不同的作用。通过将单细胞数据与两个大型队列的批量测序相结合，我们确定了 TPH、CD8 细胞、CD16 单核细胞和 DC 之间的相互作用，这些相互作用强烈促进了 RA 关节的局部促炎环境。值得注意的是，肿胀的 28 关节计数与这种免疫环境的相关性比其他疾病活动指标更为显著。免疫环境从 PBMC 到 SF 发生了显著变化，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。通过将单细胞数据与两个大型队列相结合，我们揭示了特定免疫细胞群与临床特征之间的关联。这种整合提供了一种快速、精确的方法来评估局部免疫激活，为 RA 中发挥作用的病理生理机制提供了有价值的见解。
