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Extended report
IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, which contribute to the Th17-axis in ankylosing spondylitis
  1. Eric Gracey1,2,
  2. Zoya Qaiyum1,2,
  3. Ibrahim Almaghlouth2,
  4. Daeria Lawson2,
  5. Susan Karki2,
  6. Naga Avvaru2,
  7. Zhenbo Zhang2,
  8. Yuchen Yao1,2,
  9. Vidya Ranganathan2,
  10. Yuriy Baglaenko1,2,
  11. Robert D Inman1,2
  1. 1Department of Immunology, University of Toronto, Toronto, Ontario, Canada
  2. 2Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
  1. Correspondence to Professor Robert D Inman, Toronto Western Hospital, Krembil Discovery Tower, 5th Floor 5KD412, 60 Leonard Avenue, Toronto, Ontario, Canada M5T 2S8; Robert.Inman{at}uhn.ca

Abstract

Objective Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin in which interleukin (IL) 17 has been genetically and therapeutically recognised as a key player. Identification of the cellular sources and inducers of IL-17 is crucial in our understanding of the drivers of inflammation in AS. Recently, mucosal-associated invariant T (MAIT) cells have been implicated in autoimmune diseases. Their gut origin, effector phenotype and expression of multiple AS-associated genes, such as IL7R and IL23R, makes them potential contributors to the pathogenesis of AS.

Methods Mononuclear cells from patients with AS, healthy controls (HCs) and patients with rheumatoid arthritis were isolated from blood and synovial fluid (SF). Flow cytometry was used to identify MAIT cells. Phenotype was assessed by intracellular staining for cytokines and granzyme. Function was assessed by antigen-specific stimulation using Salmonella, or antigen non-specific activation via priming with IL-7 or IL-23.

Results MAIT cells were reduced in frequency in the blood of patients with AS compared with HCs, yet patients with AS had an elevated frequency IL-17A+ MAIT cells. There was an enrichment of MAIT cells in SF, which had an exaggerated IL-17 phenotype. IL-17 elevation in AS MAIT cells was dependent on priming with IL-7 but not IL-23 or antigen stimulation. The AS-associated IL7R single nucleotide polymorphism (SNP), rs11742270, had no effect on IL-7R expression or function in the experiments performed.

Conclusions This study reveals a potential role for MAIT cells in patients with AS and is the first linking IL-7 to the elevated IL-17 profile in patients through the AS-associated risk gene IL7R.

  • Ankylosing Spondylitis
  • T Cells
  • Cytokines
  • Gene Polymorphism

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Footnotes

  • Handling editor Tore K Kvien

  • Contributors EG and RDI designed experiments. EG, ZQ, IA, SK, NA and YY performed experiments. EG, ZQ, DL, ZZ, VR, YB and RDI analysed and interpreted data. DL facilitated patient recruitment and procurement of patient data. EG and RDI wrote the manuscript. All authors agreed to publish the data and reviewed the manuscript.

  • Funding Canadian Institutes of Health Research (CIHR), and the Arthritis Research Center.

  • Competing interests None declared.

  • Ethics approval University Health Network.

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

  • Data sharing statement EG and RDI have full access to the data and take responsibility for the integrity of analysis. Data available upon request.

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