Format

Send to

Choose Destination
Ann Rheum Dis. 2019 Nov;78(11):1566-1575. doi: 10.1136/annrheumdis-2019-215349. Epub 2019 Aug 30.

Integrin and transcriptomic profiles identify a distinctive synovial CD8+ T cell subpopulation in spondyloarthritis.

Qaiyum Z1,2, Gracey E1,2, Yao Y1,2, Inman RD3,2,4.

Author information

1
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
2
Division Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
3
Department of Immunology, University of Toronto, Toronto, Ontario, Canada robert.inman@uhn.ca.
4
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

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.

KEYWORDS:

Ankylosing Spondylitis; CyTOF; RNA-seq; integrins

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center