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Details

Autor(en) / Beteiligte
Titel
Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry
Ist Teil von
  • Nature immunology, 2019-07, Vol.20 (7), p.928-942
Ort / Verlag
United States
Erscheinungsjahr
2019
Quelle
MEDLINE
Beschreibungen/Notizen
  • To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90) HLA-DRA sublining fibroblasts, IL1B pro-inflammatory monocytes, ITGAX TBX21 autoimmune-associated B cells and PDCD1 peripheral helper T (T ) cells and follicular helper T (T ) cells. We defined distinct subsets of CD8 T cells characterized by GZMK , GZMB , and GNLY phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1 HLA-DRA fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.

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