Understanding Immune Cell Changes in Juvenile Idiopathic Arthritis
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Understanding Immune Cell Changes in Juvenile Idiopathic Arthritis

01.07.2025 Compuscript Ltd

Juvenile idiopathic arthritis (JIA), a type of arthritis commonly occurring in children, is a chronic, inflammatory condition that affects the joints, causing pain, swelling, stiffness, and limiting the range of motion. An imbalance between the regulatory and effector immune cells, primarily driven by the adaptive immune system and induced by both genetic and environmental factors, contributes to the pathogenesis of JIA.

A recent study published by researchers from the Children's Hospital of Chongqing Medical University in the Genes & Diseases journal analyzed the single-cell transcriptomes of immune cells in JIA patients, particularly the sJIA and non-sJIA subtypes, to understand the immune response, both pathogenic and protective, in JIA progression.

Droplet-based single-cell RNA sequencing of peripheral blood mononuclear cells from 14 JIA patients and four healthy controls (HCs) showed an increase in the levels of monocytes, monocyte-derived dendritic cells, and platelets in JIA, along with a more pronounced pro-inflammatory response in JIA patients, particularly in sJIA versus non-sJIA subtypes.

A comparison of CD4+ cell transcriptomic profiles of sJIA, non-sJIA, and HC cells showed enrichment of DEGs associated with regulating intrinsic apoptotic signaling and VEGFA/VEGFR2 signaling pathways in the sJIA and non-sJIA groups. Similarly, the CD8+ transcriptomic profiles of the three groups showed a stronger inflammatory response, lymphocyte migration, and cytotoxicity in the sJIA subtype compared to non-sJIA, while T-cell apoptosis was higher in non-sJIA.

Additionally, the B-cell response to IFN was stronger in sJIA than in non-sJIA, which suggests that while VEGFA/VEGFR2 signaling is associated with JIA pathogenesis, IFN may be one of the factors contributing to the different clinical manifestations of sJIA and non-sJIA. Furthermore, non-classical monocytes were found only in the sJIA subtype, implicating its pathogenic role in sJIA.

CellChat analysis revealed that interactions between the CD4+ and CD8+ T cells, B cells, monocytes, and NK cells with other cell populations were abundant in both sJIA and non-sJIA cases, and macrophage MIF was expressed abundantly in all cell types. This study identified a new ligand-receptor pair, MIF (CD74–CXCR2), in the sJIA subtype, whose ligand CXCR2 is expressed only in monocytes. The authors suggest that MIF (CD74–CXCR2) may serve as an indicator to distinguish the sJIA from non-sJIA subtypes.

In conclusion, this study, the first to characterize the single-cell transcriptomic profile of immune cells in different subtypes of primary JIA, holds significant implications for the precise diagnosis and classification of JIA and may guide the development of personalized treatment strategies for JIA patients.

Reference

Title of the original paper: Single-cell landscape of immunological responses in patients with juvenile idiopathic arthritis

Journal: Genes & Diseases

Genes & Diseases is a 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.

DOI: https://doi.org/10.1016/j.gendis.2025.101577

Funding Information:
National Key Research and Development Program of China (No. 2021YFC2702003)

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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is 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.

Scopus CiteScore: 8.4 | Impact Factor: 9.4

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01.07.2025 Compuscript Ltd
Regions: Europe, Ireland, Asia, China
Keywords: Health, Medical, Science, Life Sciences

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