ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1916

Heightened MAIT Cell Sensitivity to MR1 Ligands Could Impact Control of Dysbiosis in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

Diahann Jansen1, Elizabeth Klinken1, Hendrik Nel2, Soi Cheng Law2, Helen Benham3,4,5, Lisa Cummins6, Matthew Brown7, Tony Kenna2, Ligong Liu8, David Fairlie8, Jamie Rossjohn9,10,11, Mark Morrison3, Ranjeny Thomas3, Paraic O Cuiv1, James McCluskey12 and Alexandra Corbett12, 1The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, Australia, 2The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia, 3Translational Research Institute, The University of Queensland Diamantina Institute, Woolloongabba, Australia, 4University of Queensland School of Medicine, Brisbane, Australia, 5Rheumatology, Princess Alexandra Hospital, Woolloongabba, Australia, 6Princess Alexandra Hospital, Woolloongabba, Australia, 7Queensland University of Technology, Brisbane, Australia, 8Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia, 9Infection and Immunity Program, Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia, 10Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom, 11Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Australia, 12Department of Microbiology & Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: , , ,

Session Information

Date: Monday, November 14, 2016

Title: T Cell Biology and Targets in Autoimmune Disease - Poster Session I

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Mucosal associated invariant T (MAIT) cells are an innate-like lymphocyte population predominant at mucosal sites, which express a semi-invariant T cell receptor restricted to the MHC class I-like molecule, MR1. MR1 presents ligands derived from the riboflavin synthesis pathway, common to a range of bacteria and yeast. There is evidence in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) for oral and/or gastrointestinal microbial dysbiosis. However the mechanisms underlying these disease associations are unclear. We analyzed how the response of MAIT cells to MR1 ligand might influence the development of dysbiosis.

Methods: We compared the frequency of CD3+CD4–CD161hiTRAV1-2+ PB MAIT cells in 45 RA, 10 AS patients, and 38 healthy controls (HC). We investigated the frequency of 5-OP-RU-specific MAIT cells using MR1-tetramers and analyzed cellular activation of MAIT cells in arthritis patients and HC after stimulation with 5-OP-RU ligand. We identified compositional variations in the oral microbiome of RA patients, and assessed whether these variations are reflected in riboflavin biosynthesis pathways

Results: Bacterial species capable of riboflavin synthesis and thus MAIT cell ligand production, including Streptococcus infantilis, Rothia dentocarisosa, Rothia mucilaginosa and Prevotella melaninogenica were more abundant in the oral microbiome of RA patients than HC. We observed no difference in MAIT cell frequencies when comparing HC, RA and AS patient groups matched for age and sex. However, the proportion of PB MAIT cells declined with age in all groups and accordingly, was significantly lower in patients with late- rather than early-onset RA. PB MAIT cells were constitutively more activated than conventional T cells. The frequency of 5-OP-RU-specific PB MAIT cells ranged from 0.8-8%. When stimulated ex vivo with the riboflavin metabolite 5-OP-RU, PB MAIT cells upregulated CD69. In response to 5-OP-RU, approximately 50% of MAIT cells secreted TNF and 10% secreted IFN-g, while less than 1% secreted IL-17. The ligand was highly specific, as conventional T cells in the same culture were not activated. When compared to HC MAIT cells, MAIT cells from arthritis patients were more susceptible to apoptosis in response to 5-OP-RU, and residual live cells expressed lower levels of CD69 or TNF than HC.

Conclusion: PB MAIT cells decline with age in arthritis patients similar to HC. MAIT cells of arthritis patients have greater susceptibility to MR1 ligand-induced cell death in vitro and the surviving cells have lower capacity for cytokine production. Certain bacterial species enriched at the RA mucosal sites are capable of riboflavin biosynthesis, and presumptively, the formation and release of MR1 ligands, which could impact control of dysbiosis by MAIT cells.

Disclosure: D. Jansen, None; E. Klinken, None; H. Nel, None; S. C. Law, None; H. Benham, None; L. Cummins, None; M. Brown, None; T. Kenna, None; L. Liu, None; D. Fairlie, None; J. Rossjohn, None; M. Morrison, None; R. Thomas, None; P. O Cuiv, None; J. McCluskey, None; A. Corbett, None.

To cite this abstract in AMA style:

Jansen D, Klinken E, Nel H, Law SC, Benham H, Cummins L, Brown M, Kenna T, Liu L, Fairlie D, Rossjohn J, Morrison M, Thomas R, O Cuiv P, McCluskey J, Corbett A. Heightened MAIT Cell Sensitivity to MR1 Ligands Could Impact Control of Dysbiosis in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/heightened-mait-cell-sensitivity-to-mr1-ligands-could-impact-control-of-dysbiosis-in-patients-with-rheumatoid-arthritis-and-ankylosing-spondylitis/. Accessed .

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