Journal article
Ex vivo mass cytometry analysis reveals a profound myeloid proinflammatory signature in psoriatic arthritis synovial fluid
- Abstract:
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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 h. 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 and single-cell RNA-seq, and 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 amongst those most highly upregulated by PsA monocytes/macrophages; 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.
Competing Interest Statement
The authors have declared no competing interest.
- Publication status:
- Published
- Peer review status:
- Not peer reviewed
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(Preview, Submitted manuscript under review, pdf, 10.4MB, Terms of use)
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- Publisher copy:
- 10.1101/2021.03.04.433903
Authors
- Publisher:
- Cold Spring Harbor Laboratory
- Journal:
- bioRxiv More from this journal
- Publication date:
- 2021-03-04
- DOI:
- Language:
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English
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- Pubs id:
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1167573
- Local pid:
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pubs:1167573
- Deposit date:
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2023-10-03
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- Copyright holder:
- Yager et al.
- Copyright date:
- 2021
- Rights statement:
- The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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