Drivers of heterogeneity in synovial fibroblasts in rheumatoid arthritis Journal Article
| Authors: | Smith, M. H.; Gao, V. R.; Periyakoil, P. K.; Kochen, A.; DiCarlo, E. F.; Goodman, S. M.; Norman, T. M.; Donlin, L. T.; Leslie, C. S.; Rudensky, A. Y. |
| Article Title: | Drivers of heterogeneity in synovial fibroblasts in rheumatoid arthritis |
| Abstract: | 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. © 2023, The Author(s). |
| Keywords: | genetics; metabolism; cells, cultured; interleukin 1beta; transcriptomics; cell heterogeneity; cytokine; cytokines; gamma interferon; cell culture; fibroblast; fibroblasts; rheumatoid arthritis; cell expansion; tumor necrosis factor; synovial membrane; synoviocyte; synovitis; synovium; arthritis, rheumatoid; humans; human; article; cytokine signaling; single cell rna seq; cell signaling assay |
| Journal Title: | Nature Immunology |
| Volume: | 24 |
| Issue: | 7 |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-07-01 |
| Start Page: | 1200 |
| End Page: | 1210 |
| Language: | English |
| DOI: | 10.1038/s41590-023-01527-9 |
| PUBMED: | 37277655 |
| PROVIDER: | scopus |
| PMCID: | PMC10307631 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding author is MSK authors Christina S. Leslie and Alexander Y. Rudensky -- Source: Scopus |
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