Drivers of heterogeneity in synovial fibroblasts in rheumatoid arthritis.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
26
02
2022
accepted:
04
05
2023
medline:
30
6
2023
pubmed:
6
6
2023
entrez:
5
6
2023
Statut:
ppublish
Résumé
Inflammation of non-barrier immunologically quiescent tissues is associated with a massive influx of blood-borne innate and adaptive immune cells. Cues from the latter are likely to alter and expand activated states of the resident cells. However, local communications between immigrant and resident cell types in human inflammatory disease remain poorly understood. Here, we explored drivers of fibroblast-like synoviocyte (FLS) heterogeneity in inflamed joints of patients with rheumatoid arthritis using paired single-cell RNA and ATAC sequencing, multiplexed imaging and spatial transcriptomics along with in vitro modeling of cell-extrinsic factor signaling. These analyses suggest that local exposures to myeloid and T cell-derived cytokines, TNF, IFN-γ, IL-1β or lack thereof, drive four distinct FLS states some of which closely resemble fibroblast states in other disease-affected tissues including skin and colon. Our results highlight a role for concurrent, spatially distributed cytokine signaling within the inflamed synovium.
Identifiants
pubmed: 37277655
doi: 10.1038/s41590-023-01527-9
pii: 10.1038/s41590-023-01527-9
pmc: PMC10307631
doi:
Substances chimiques
Cytokines
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1200-1210Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG012103
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023. The Author(s).
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