The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Distinct fibroblast subsets drive inflammation and damage in arthritis
Open accessAbstract
The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune-mediated inflammatory diseases (IMIDs)1,2. However, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue-driven processes observed in IMIDs, such as inflammation and damage 3-5. Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of fibroblast activation protein-α (FAPα)+ fibroblasts suppressed both inflammation and bone erosions in mouse models of resolving and persistent arthritis. Single-cell transcriptional analysis identified two distinct fibroblast subsets within the FAPα+ population: FAPα+THY1+ immune effector fibroblasts located in the synovial sub-lining, and FAPα+THY1- destructive fibroblasts restricted to the synovial lining layer. When adoptively transferred into the joint, FAPα+THY1- fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation, whereas transfer of FAPα+ THY1+ fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell-based therapies aimed at modulating inflammation and tissue damage.
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“While single-cell sequencing indicates common traits are preserved49–51, it will become increasingly pressing to define common and specific effects of CAFs.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [50]
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“Overwhelming evidence now points to a degree of specialization among CAFs, which may reflect the increasingly appreciated specialization of normal fibroblasts19,50.”
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“Recent studies have implicated a range of mesenchymal progenitor cells (MPs) in the initiation and propagation of fibrosis28–30.”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [28]
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Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma
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Synovitis score: discrimination between chronic low‐grade and high‐grade synovitis
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A framework for advancing our understanding of cancer-associated fibroblasts
Sahai, E., Astsaturov, I., Cukierman, E., DeNardo, D. G., Egeblad, M., Evans, R. M., Fearon, D., Greten, F. R., Hingorani, S. R., Hunter, T., et al. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0238-1 · Cited by 3,863
Self-citationFibrosis: from mechanisms to medicines
Henderson, N. C., Rieder, F., & Wynn, T. A. (2020) · Nature · doi:10.1038/s41586-020-2938-9 · Cited by 1,868
Pattern recognition receptors in health and diseases
Li, D., & Wu, M. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00687-0 · Cited by 1,961
Diversity and biology of cancer-associated fibroblasts
Biffi, G., & Tuveson, D. A. (2021) · Physiological Reviews · doi:10.1152/physrev.00048.2019 · Cited by 1,265
Cross-tissue organization of the fibroblast lineage
Buechler, M. B., Pradhan, R., Krishnamurty, A. T., Cox, C. B., Calviello, A. K., Wang, A. W., Yang, Y. A., Tam, L., Caothien, R. H., Roose‐Girma, M., et al. (2021) · Nature · doi:10.1038/s41586-021-03549-5 · Cited by 1,100
Metadata
- Authors
- Croft, A. P., Campos, J., Jansen, K., Turner, J. D., Marshall, J., Attar, M., Savary, L., Wehmeyer, C., Naylor, A. J., Kemble, S., Begum, J., Dürholz, K., Perlman, H., Barone, F., McGettrick, H. M., Fearon, D. T., Wei, K., Raychaudhuri, S., Korsunsky, I., Brenner, M. B., Coles, M., Sansom, S. N., Filer, A., & Buckley, C. D.
- Affiliations
- Queen Elizabeth Hospital Birmingham (GB)
- University of Oxford (GB)
- University of Münster (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Northwestern University (US)
- Cold Spring Harbor Laboratory (US)
- Brigham and Women's Hospital (US)
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Corresponding author
- Buckley, Christopher D.
- ORCID
- Croft, Adam P.
- Campos, Joana
- Jansen, Kathrin
- Turner, Jason D.
- Marshall, Jennifer
- Attar, Moustafa
- Wehmeyer, Corinna
- Naylor, Amy J.
- Kemble, Samuel
- Begum, Jenefa
- Perlman, Harris
- Barone, Francesca
- McGettrick, Helen M.
- Fearon, Douglas T.
- Wei, Kevin
- Raychaudhuri, Soumya
- Korsunsky, Ilya
- Brenner, Michael B.
- Coles, Mark
- Sansom, Stephen N.
- Filer, Andrew
- Buckley, Christopher D.
- Venue
- Nature
- Published
- 2019-05-29
- Volume
- 570
- Issue
- 7760
- Pages
- 246-251
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6690841
- OpenAlex
- W2944564829
- Cited by
- 976
- References
- 28
- Citations by year
- 2026: 147 · 2025: 144 · 2024: 137 · 2023: 134 · 2022: 128 · 2021: 153 · 2020: 94 · 2019: 36
- FWCI
- 78.26
- Type
- journal article
- Language
- en
- Update notices
- correction (2025-12-12)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (WT104551MA)
- Kennedy Trust for Rheumatology Research (KENN161701, KENN161703)
- National Institute for Health and Care Research (bircrf-2012-1, NF-SI-0617-10128, CL-2018-09-001)
- Academy of Medical Sciences (SGL021\1029)
- Versus Arthritis (19791, 21743, 20015, 14476, 19899, 18547, 21236)
- National Institutes of Health (5r01ar063759-07)
- Medical Research Council (MR/S025308/1, MR/N026977/1)
- National Heart, Lung, and Blood Institute (R01HL134375)
- National Human Genome Research Institute (U01HG009379)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (UH2AR067677, R01-AR063759)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- arthritis, fibroblast activation protein, CD90, synovial lining, bone erosion, cartilage damage, joint inflammation, tissue damage, adoptive transfer, immune-mediated inflammatory diseases
- MeSH terms
- RNA-Seq, Fibroblast Activation Protein Alpha, Animals, Arthritis, Rheumatoid, Bone and Bones, Female, Fibroblasts, Humans, Inflammation, Joints, Male, Membrane Proteins, Endopeptidases, Serine Endopeptidases, Synovial Membrane, Gelatinases, Thy-1 Antigens, Mice, Single-Cell Analysis
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