Liu Yun, Luo Xiwen, Yang Liuqing, Luo Qiang, Luo Xiya, Xu Li, Wang Yating, An Yunfei, Cun Yupeng, Tang Xuemei
Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
Genes Dis. 2025 Mar 3;12(5):101577. doi: 10.1016/j.gendis.2025.101577. eCollection 2025 Sep.
The study aimed to analyze the single-cell transcriptomes of immune cells in juvenile idiopathic arthritis (JIA) patients to understand the cellular heterogeneity within the immune system. Peripheral blood samples from fourteen JIA patients and four healthy individuals were subjected to single-cell RNA sequencing. Various subtypes of JIA were included in the patient cohort. Functional analyses, such as pseudotime trajectories and cell communication studies, were conducted to uncover immune cell changes in JIA patients. Results showed disrupted interferon and acute inflammatory responses in most cell types of JIA patients, with particularly intense responses in systemic JIA (sJIA) patients versus non-sJIA patients. Pseudotime analysis of CD4 T, CD8 T, B, and myeloid cells revealed that the functions of each cytokine production, cytotoxicity, and the processing and presentation of antigens were progressively strengthened, while the regulation of nuclear factor kappa B (NF-κB)-related pathways was weaker in CD4 T and CD8 T cells than in non-JIA. Reclustering analysis of myeloid cells highlighted interferon-related functions predominantly in non-classical monocytes of sJIA patients. Additionally, cell communication analysis identified unique ligand-receptor pairs in sJIA, suggesting potential roles in disease progression. In conclusion, interferon disorders are evident across various immune cell types in JIA patients, with stronger responses observed in sJIA patients. The ligand-receptor pairs involving migration inhibitory factor (MIF) and CXCR7/CD44 may contribute to differing joint symptoms between sJIA and non-sJIA patients. Moreover, non-classical monocytes and the CXCR2 receptor in MIF signaling may play crucial roles in sJIA progression.
该研究旨在分析青少年特发性关节炎（JIA）患者免疫细胞的单细胞转录组，以了解免疫系统内的细胞异质性。对14名JIA患者和4名健康个体的外周血样本进行单细胞RNA测序。患者队列中纳入了各种JIA亚型。进行了诸如拟时间轨迹和细胞通讯研究等功能分析，以揭示JIA患者免疫细胞的变化。结果显示，JIA患者的大多数细胞类型中干扰素和急性炎症反应受到破坏，与非系统性JIA（sJIA）患者相比，系统性JIA（sJIA）患者的反应尤为强烈。对CD4 T细胞、CD8 T细胞、B细胞和髓样细胞的拟时间分析表明，每种细胞因子产生、细胞毒性以及抗原加工和呈递的功能逐渐增强，而CD4 T细胞和CD8 T细胞中核因子κB（NF-κB）相关途径的调节比非JIA患者弱。髓样细胞的再聚类分析突出了sJIA患者非经典单核细胞中主要的干扰素相关功能。此外，细胞通讯分析确定了sJIA中独特的配体-受体对，提示其在疾病进展中的潜在作用。总之，JIA患者的各种免疫细胞类型中均明显存在干扰素紊乱，sJIA患者中观察到更强的反应。涉及迁移抑制因子（MIF）和CXCR7/CD44的配体-受体对可能导致sJIA和非sJIA患者之间不同的关节症状。此外，非经典单核细胞和MIF信号通路中的CXCR2受体可能在sJIA进展中起关键作用。
