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Subcellular spatial transcriptomics reveals immune-stromal crosstalk within the synovium of patients with juvenile idiopathic arthritis.

作者信息

Inamo Jun, Fierkens Roselyn, CLay Michael R, Jonsson Anna Helena, Lin Clara, Hayes Kari, Rogers Nathan, Leach Heather, Yomogida Kentaro

机构信息

Department of Biomedical Informatics, Center for Health Artificial Intelligence, University of Colorado School of Medicine, Aurora, CO, United States of America.

Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, United States of America.

出版信息

medRxiv. 2025 Aug 8:2025.08.05.25332835. doi: 10.1101/2025.08.05.25332835.


DOI:10.1101/2025.08.05.25332835
PMID:40894156
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12396606/
Abstract

Juvenile idiopathic arthritis (JIA) is the most prevalent chronic inflammatory arthritis of childhood, yet the spatial organization in the synovium remains poorly understood. Here, we perform subcellular-resolution spatial transcriptomic profiling of synovial tissue from patients with active JIA. We identify diverse immune and stromal cell populations and reconstruct spatially defined cellular niches. Applying a newly developed spatial colocalization analysis pipeline, we uncover microanatomical structures, including endothelial-fibroblast interactions mediated by NOTCH signalling, and a CXCL9-CXCR3 signaling axis between inflammatory macrophages and CD8+ T cells, alongside the characterization of other resident macrophage subsets. We also detect and characterize tertiary lymphoid structures marked by CXCL13-CXCR5 and CCL19-mediated signaling from Tph cells and immunoregulatory dendritic cells, analogous to those observed in other autoimmune diseases. Finally, comparative analysis with rheumatoid arthritis reveals JIA-enriched cell states, including and sublining fibroblasts, suggesting potentially differential inflammatory programs in pediatric versus adult arthritis. These findings provide a spatially resolved molecular framework of JIA synovitis and introduce a generalizable computational pipeline for spatial colocalization analysis in tissue inflammation.

摘要

相似文献

[1]
Subcellular spatial transcriptomics reveals immune-stromal crosstalk within the synovium of patients with juvenile idiopathic arthritis.

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[2]
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本文引用的文献

[1]
Synovial tissue atlas in juvenile idiopathic arthritis reveals pathogenic niches associated with disease severity.

Sci Transl Med. 2025-7-2

[2]
Spatially resolved mapping of cells associated with human complex traits.

Nature. 2025-5

[3]
Granzyme K activates the entire complement cascade.

Nature. 2025-5

[4]
GZMK-expressing CD8 T cells promote recurrent airway inflammatory diseases.

Nature. 2025-2

[5]
Childhood-onset lupus nephritis is characterized by complex interactions between kidney stroma and infiltrating immune cells.

Sci Transl Med. 2024-11-27

[6]
Macrophages and nociceptor neurons form a sentinel unit around fenestrated capillaries to defend the synovium from circulating immune challenge.

Nat Immunol. 2024-12

[7]
CellChat for systematic analysis of cell-cell communication from single-cell transcriptomics.

Nat Protoc. 2025-1

[8]
A Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of PF-06835375, a C-X-C chemokine receptor type 5 directed antibody, in patients with systemic lupus erythematosus or rheumatoid arthritis.

Arthritis Res Ther. 2024-6-6

[9]
TREM2 promotes macrophage polarization from M1 to M2 and suppresses osteoarthritis through the NF-κB/CXCL3 axis.

Int J Biol Sci. 2024-3-11

[10]
Metabolic targeting of cancer associated fibroblasts overcomes T-cell exclusion and chemoresistance in soft-tissue sarcomas.

Nat Commun. 2024-3-20

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