Single-cell landscape of immunological responses in patients with juvenile idiopathic arthritis

IF 6.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yun Liu , Xiwen Luo , Liuqing Yang , Qiang Luo , Xiya Luo , Li Xu , Yating Wang , Yunfei An , Yupeng Cun , Xuemei Tang
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Abstract

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.
青少年特发性关节炎患者免疫反应的单细胞景观
本研究旨在分析幼年特发性关节炎(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例JIA患者和4例健康人的外周血进行单细胞RNA测序。不同亚型的JIA被纳入患者队列。通过功能分析,如伪时间轨迹和细胞通讯研究,揭示JIA患者免疫细胞的变化。结果显示,大多数JIA患者的细胞类型干扰素和急性炎症反应被破坏,系统性JIA (sJIA)患者与非sJIA患者相比,反应特别强烈。CD4+ T、CD8+ T、B和骨髓细胞的伪时间分析显示,CD4+ T和CD8+ T细胞中各细胞因子的产生、细胞毒性和抗原的加工和呈递功能逐渐增强,而核因子κB (NF-κB)相关通路的调控在CD4+ T和CD8+ T细胞中较非jia细胞弱。髓细胞的重新聚类分析强调干扰素相关功能主要存在于sJIA患者的非经典单核细胞中。此外,细胞通讯分析发现了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,干扰素紊乱在JIA患者的各种免疫细胞类型中都很明显,在sJIA患者中观察到更强的应答。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患者关节症状的不同。此外,MIF信号传导中的非经典单核细胞和CXCR2受体可能在sJIA进展中发挥关键作用。
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来源期刊
Genes & Diseases
Genes & Diseases Multiple-
CiteScore
7.30
自引率
0.00%
发文量
347
审稿时长
49 days
期刊介绍: Genes & Diseases is an international journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch. Aims and Scopes Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis will be placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
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