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| Status |
Public on Jan 16, 2024 |
| Title |
Molecular reframing of fibroblasts during resolution of arthritis [RNA] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Fibroblasts are key orchestrators of inflammation. Little is known whether these cells change phenotype during resolution of inflammation. We adopted a method to visualise fibroblast activation during inflammation in humans in vivo, which is based on a fibroblast activation protein (FAP) tracer detected by positron emission tomography (PET). While tracer accumulation was high in active arthritis, it decreased significantly after TNF- and IL-17A inhibition. Biopsy-based scRNA-seq analyses in experimental arthritis demonstrated that FAP signal reduction reflected a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalisation) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalisation). Spatial transcriptomics of human joints revealed that pro-resolving niches of CD200+DKK3+ fibroblasts clustered with innate lymphoid cells (ILC)2, whereas MMP3+/IL6+ fibroblasts were co-localised with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilised the ILC2 phenotype and induced resolution of arthritis via CD200/CD200R1 pathway. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.
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| Overall design |
Total RNA was isolated from arthroscopic synovial biopsies of patients with rheumatoid arthritis (RA; N=10) and psoriatic arthritis (PsA; N=8) and bulk RNA sequencing was performed.
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| Contributor(s) |
Rauber S, Mohammdian H, Hanlon M, Fearon U, Veale D, Ramming A |
| Citation(s) |
38396288 |
| |
| Submission date |
Apr 04, 2023 |
| Last update date |
Mar 12, 2024 |
| Contact name |
Hashem Mohammadian |
| Organization name |
University of Erlangen-Nürnberg
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| Department |
Department of Medicine 3 - Rheumatology and Immunology
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| Street address |
Ulmenweg 18
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| City |
Erlangen |
| ZIP/Postal code |
91054 |
| Country |
Germany |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE228982 |
Molecular reframing of fibroblasts during resolution of arthritis |
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| Relations |
| BioProject |
PRJNA952240 |
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