Journal Article

IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, which contribute to the Th17-axis in ankylosing spondylitis

Qaiyum, Zoya, Inman, Robert D, Karki, Susan, Gracey, Eric, Zhang, Zhenbo, Almaghlouth, Ibrahim, Baglaenko, Yuriy, Ranganathan, Vidya, Avvaru, Naga, Lawson, Daeria, Yao, Yuchen

2016

Overview

ObjectiveAnkylosing 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.MethodsMononuclear 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.ResultsMAIT 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.ConclusionsThis 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.

• Publisher: Elsevier Limited
• Subject: Adult / Aged / Antibodies / Antigens / Arthritis / Arthritis, Rheumatoid - blood / Arthritis, Rheumatoid - immunology / Bacteria / Case-Control Studies / Cell growth / Cytokines / Experiments / Female / Flow Cytometry / Humans / Inflammatory bowel disease / Interleukin-17 - metabolism / Interleukin-23 - metabolism / Interleukin-7 - metabolism / Lymphocyte Activation / Lymphocytes / Male / Middle Aged / Mucosal-Associated Invariant T Cells - immunology / Pilot projects / Polymorphism, Single Nucleotide / Receptors, Interleukin-7 - genetics / Receptors, Interleukin-7 - metabolism / Salmonella / Spondylitis, Ankylosing - blood / Spondylitis, Ankylosing - genetics / Spondylitis, Ankylosing - immunology / Synovial Fluid - cytology / T cell receptors / Th17 Cells - immunology / Tumor necrosis factor-TNF