title: IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, which contribute to the Th17-axis in ankylosing spondylitis.
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.
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Gracey
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Qaiyum
authors.affiliation: Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Almaghlouth
authors.affiliation: Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Daeria
authors.initials: D
authors.lastname: Lawson
authors.affiliation: Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Karki
authors.affiliation: Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Naga
authors.initials: N
authors.lastname: Avvaru
authors.affiliation: Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Vidya
authors.initials: V
authors.lastname: Ranganathan
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Baglaenko
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Inman
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D000072336:Mucosal-Associated Invariant T Cells / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000235:genetics / Q000276:immunology*; D013582:Synovial Fluid / Q000166:cytology; D058504:Th17 Cells / Q000276:immunology
chemical_list: C508717:IL17A protein, human; C508605:IL7 protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D015851:Interleukin-7; D020395:Receptors, Interleukin-7
keywords: Ankylosing Spondylitis; Cytokines; Gene Polymorphism; T Cells