Journal article
Synovial matrix turnover controls immune cell spatial patterning in inflammation resolution
- Abstract:
- Immune-mediated inflammatory diseases remain plagued by poor treatment responses and lack curative therapies. Convergent findings suggest a role for stromal compartment and extracellular matrix composition dysregulation. Using rheumatoid arthritis as a model, we define an analytical pipeline combining transcriptomic, proteomic and degradomic analysis to characterise disease activity-specific matrix perturbations. This revealed synergistic contributions from fibroblasts and myeloid cells to matrix composition, with fibroblast subsets defining distinct subsynovial niches through distinct matrix expression profiles. Transcriptional dysregulation of collagen VI was found to be a feature of RA activity, with collagen VI protein accumulation linked to remission-associated states. Spatial analysis and in vitro migration showed collagen VI inhibits immune ingress, confining infiltrating cells to perivascular pockets termed "COL6 dark" zones. Matrix degradation-associated monocytes were found at the leading edge of these zones, expanding immune-permissive niches, and releasing RA-associated collagen VI fragments. Our work reveals how dynamic matrix remodelling can in turn limit, and enable, cell immigration in RA, identifying a new mechanism controlling tissuelevel disease activity.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Version of record, pdf, 4.9MB, Terms of use)
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- Publisher copy:
- 10.1038/s44320-025-00149-7
Authors
- Publisher:
- EMBO Press
- Journal:
- Molecular Systems Biology More from this journal
- Publication date:
- 2025-09-22
- Acceptance date:
- 2025-09-02
- DOI:
- EISSN:
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1744-4292
- Language:
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English
- Keywords:
- Pubs id:
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2287710
- Local pid:
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pubs:2287710
- Deposit date:
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2025-09-12
Terms of use
- Copyright holder:
- Richard et al
- Copyright date:
- 2025
- Rights statement:
- © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0International License, which permits use, sharing, adaptation, distribution andreproduction in any medium or format, as long as you give appropriate credit tothe original author(s) and the source, provide a link to the Creative Commonslicence, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons licence,unless indicated otherwise in a credit line to the material. If material is notincluded in the article’s Creative Commons licence and your intended use is notpermitted by statutory regulation or exceeds the permitted use, you will need toobtain permission directly from the copyright holder. To view a copy of thislicence, visit http://creativecommons.org/licenses/by/4.0/. Creative Com-mons Public Domain Dedication waiver http://creativecommons.org/public-domain/zero/1.0/ applies to the data associated with this article, unlessotherwise stated in a credit line to the data, but does not extend to the graphicalor creative elements of illustrations, charts, or figures. This waiver removes legalbarriers to the re-use and mining of research data. According to standardscholarly practice, it is recommended to provide appropriate citation andattribution whenever technically possible.
- Licence:
- CC Attribution (CC BY)
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