Journal article
A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution
- Abstract:
- Frozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most fibrotic diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTKlowCD48+ macrophages and MERTK + LYVE1 + MRC1+ macrophages enriched for negative regulators of inflammation which co-exist in frozen shoulder capsule tissues. Micro-cultures of patient-derived cells identify integrin-mediated cell-matrix interactions between MERTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in frozen shoulder resolution. Cross-tissue analysis reveals a shared gene expression cassette between shoulder capsule MERTK+ macrophages and a respective population enriched in synovial tissues of rheumatoid arthritis patients in disease remission, supporting the concept that MERTK+ macrophages mediate resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identify MERTK + LYVE1 + MRC1+ macrophages and DKK3+ and POSTN+ fibroblast populations analogous to those in frozen shoulder, suggesting that the template to resolve fibrosis is established during shoulder development. Crosstalk between MerTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts could facilitate resolution of frozen shoulder, providing a basis for potential therapeutic resolution of persistent fibrotic diseases.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 5.3MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-024-45341-9
Authors
+ Versus Arthritis
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- Funder identifier:
- https://ror.org/02jkpm469
- Grant:
- 22425
- Programme:
- Versus Arthritis Career Development Fellowship
+ Wellcome Trust
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- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 222426/Z/21/Z
+ Rosetrees Trust
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- Funder identifier:
- https://ror.org/04e3zg361
- Grant:
- PGL21/10048
+ National Institute for Health Research
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- Funder identifier:
- https://ror.org/0187kwz08
- Grant:
- RTF1906\121
+ Medical Research Council
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- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- MR/S035850/1
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 15
- Issue:
- 1
- Article number:
- 1394
- Publication date:
- 2024-02-19
- Acceptance date:
- 2024-01-19
- DOI:
- EISSN:
-
2041-1723
- Language:
-
English
- Pubs id:
-
1619026
- Local pid:
-
pubs:1619026
- Deposit date:
-
2024-02-16
Terms of use
- Copyright holder:
- Ng et al.
- Copyright date:
- 2024
- Rights statement:
- © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material 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 not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Notes:
- This research was funded in whole or in part by the Medical Research Council (MR/S035850/1). For the purposes of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript (AAM) version arising from this submission.
- Licence:
- CC Attribution (CC BY)
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