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Integrin and transcriptomic profiles identify a distinctive synovial CD8+ T cell subpopulation in spondyloarthritis
  1. Zoya Qaiyum1,2,
  2. Eric Gracey1,2,
  3. YuChen Yao1,2,
  4. Robert D Inman1,2,3
  1. 1 Department of Immunology, University of Toronto, Toronto, Ontario, Canada
  2. 2 Division Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
  3. 3 Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Dr Robert D Inman, Toronto Western Hospital, 399 Bathurst St, Toronto, ON M5T 2S8, Canada; robert.inman{at}uhn.ca

Abstract

Objectives Current evidence suggests that immune events in the gut may impact joint inflammation in ankylosing spondylitis (AS) but the expression of gut-related trafficking molecules in the inflammed joint is poorly characterised. We aimed to (1) assess differential expression patterns of trafficking molecules between patients and controls, (2) generate joint-specific cellular signatures and (3) obtain transcriptomic profiles of noteworthy cell subpopulations.

Methods Male subjects under 40 years of age fulfilling the mNY criteria were recruited. The following cells were surface stained using a 36-marker mass cytometry antibody panel: (1) peripheral blood mononuclear cells from AS patients, and healthy controls; (2) synovial fluid mononuclear cells from AS and rheumatoid arthritis (RA) patients. Additionally, RNA-seq was performed on CD8+ T cell subpopulations from the synovial fluid (SF).

Results Mature CD8+ T cells were enriched in AS SF, with a distinct pattern of integrin expression (β7, CD103, CD29 and CD49a). RNA-seq analysis of SF-derived CD103+CD49a+CD8+ T cells revealed elevated TNFAIP3, GZMB, PRF1 and IL-10.

Conclusions We have identified a novel integrin-expressing mature CD8+ T cell population (CD49a+CD103+β7+CD29+) that appears to be more prevalent in AS SF than RA SF. These cells seem to possess dual cytotoxic and regulatory profiles which may play a role in AS pathogenesis.

  • Ankylosing Spondylitis
  • CyTOF
  • RNA-seq
  • integrins
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Footnotes

  • Handling editor Josef S Smolen

  • Contributors ZQ, EG and RDI were involved with study conception and design. ZQ and YY processed the blood and synovial fluid samples, while ZQ and EG performed the remainder of the experiments. ZQ, EG and RDI analysed and interpreted the data. ZQ, EG and RDI wrote the manuscript. All authors agreed to publish the data and reviewed the manuscript.

  • Funding Canadian Institutes of Health Research (CIHR) grant number 159671 Krembil Research Institute Fall 2016 Post-doctoral Fellowship recipient University of Toronto Open Fellowship.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Ethics approval Venous blood and knee synovial fluid extraction obtained under the institutional approval.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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