Tissue-destructive fibroblasts in arthritis are driven by the transcription factor ETS1. Analysis of a cross-tissue, single-cell fibroblast dataset and genetic loss-of-function approaches further suggest that ETS1-expressing fibroblasts have a universal role in pathological tissue remodeling in multiple diseases, including arthritis, colitis and cancer.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Croft, A. P. et al. Distinct fibroblast subsets drive inflammation and damage in arthritis. Nature 570, 246–251 (2019). This article shows that lining-layer THY1– fibroblasts induce bone and cartilage damage, whereas sublining-layer THY1+ fibroblasts promote inflammation.
Takeuchi, T. et al. Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (denosumab) in patients with rheumatoid arthritis on methotrexate to validate inhibitory effect on bone erosion (DRIVE)-a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial. Ann. Rheum. Dis. 75, 983–990 (2016). This multicenter, randomized, placebo-controlled phase 2 study shows that the addition of denosumab (monoclonal antibody to RANKL) to methotrexate treatment has the potential to suppress bone erosion in patients with RA.
Buechler, M. B. et al. Cross-tissue organization of the fibroblast lineage. Nature 593, 575–579 (2021). This paper presents a cross-tissue, single-cell atlas of fibroblasts from healthy and perturbed tissues and reveals the organizing principles of fibroblast lineage within and across organs.
Korsunsky, I. et al. Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases. Med 3, 1–38 (2022). This paper reveals shared pro-inflammatory fibroblasts across four chronic inflammatory diseases.
Wohlfahrt, T. et al. PU.1 controls fibroblast polarization and tissue fibrosis. Nature 566, 344–349 (2019). This paper presents a role for PU.1 in fibroblasts for driving tissue fibrosis.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Yan, M. et al. ETS1 governs pathological tissue-remodeling programs in disease-associated fibroblasts. Nat. Immunol. https://doi.org/10.1038/s41590-022-01285-0 (2022).
Rights and permissions
About this article
Cite this article
ETS1 is a key transcription factor that drives RANKL-expressing, tissue-destructive fibroblasts. Nat Immunol 23, 1303–1304 (2022). https://doi.org/10.1038/s41590-022-01298-9
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41590-022-01298-9
