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.
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 November 29, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/heightened-mait-cell-sensitivity-to-mr1-ligands-could-impact-control-of-dysbiosis-in-patients-with-rheumatoid-arthritis-and-ankylosing-spondylitis/