Bibliographic Details
| Title: |
Ex vivo mass cytometry analysis reveals a profound myeloid proinflammatory signature in psoriatic arthritis synovial fluid. |
| Authors: |
Yager, Nicole, Cole, Suzanne, Lara, Alicia Lledo, Maroof, Ash, Penkava, Frank, Knight, Julian C., Bowness, Paul, Al-Mossawi, Hussein, Lledo Lara, Alicia |
| Source: |
Annals of the Rheumatic Diseases; Dec2021, Vol. 80 Issue 12, p1559-1567, 9p |
| Subject Terms: |
CELL metabolism, PROTEIN metabolism, DENDRITIC cells, PSORIATIC arthritis, PROTEINS, FLOW cytometry, RESEARCH, RESEARCH methodology, MACROPHAGES, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, ENZYME-linked immunosorbent assay, CELLS, GENE expression profiling, T cells, INFLAMMATORY mediators, CYTOLOGY, MONOCYTES, SYNOVIAL fluid |
| Abstract: |
Objectives: A number of immune populations have been implicated in psoriatic arthritis (PsA) pathogenesis. This study used mass cytometry (CyTOF) combined with transcriptomic analysis to generate a high-dimensional dataset of matched PsA synovial fluid (SF) and blood leucocytes, with the aim of identifying cytokine production ex vivo in unstimulated lymphoid and myeloid cells.Methods: Fresh SF and paired blood were either fixed or incubated with protein transport inhibitors for 6 hours. Samples were stained with two CyTOF panels: a phenotyping panel and an intracellular panel, including antibodies to both T cell and myeloid cell secreted proteins. Transcriptomic analysis by gene array of key expanded cell populations, single-cell RNA-seq, ELISA and LEGENDplex analysis of PsA SF were also performed.Results: We observed marked changes in the myeloid compartment of PsA SF relative to blood, with expansion of intermediate monocytes, macrophages and dendritic cell populations. Classical monocytes, intermediate monocytes and macrophages spontaneously produced significant levels of the proinflammatory mediators osteopontin and CCL2 in the absence of any in vitro stimulation. By contrast minimal spontaneous cytokine production by T cells was detected. Gene expression analysis showed the genes for osteopontin and CCL2 to be among those most highly upregulated by PsA monocytes/macrophages in SF; and both proteins were elevated in PsA SF.Conclusions: Using multiomic analyses, we have generated a comprehensive cellular map of PsA SF and blood to reveal key expanded myeloid proinflammatory modules in PsA of potential pathogenic and therapeutic importance. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
