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Altered composition and phenotype of mucosal-associated invariant T cells in early untreated rheumatoid arthritis | Arthritis Research & Therapy
Description:
Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognise bacterial metabolites presented by MHC class I-related protein 1 (MR1). Bacterial dysbiosis has been implicated in auto-inflammatory disease development. We investigated MAIT cells in early, untreated rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients. Blood and synovial fluid mononuclear cells obtained from patients (SpA/RA) and controls were stimulated with fixed Escherichia coli to provide MAIT ligand. Cells were analysed by flow cytometry and MAIT cells were identified by MR1-5-OP-RU tetramers. Synovial biopsies were studied by confocal microscopy. Peripheral and synovial CD3+ MR1-tet+ MAIT cell frequencies were comparable in all groups. MAIT cells were detected in RA and SpA synovium based on CD3, CD161 and Vα7.2 expression. Peripheral RA MAIT cells were mostly CD4+ (controls 8.3%, SpA 12.3%, RA 52.6%; p < 0.001) and CD161 expression was strongly reduced (control mean fluorescence intensity (MFI) = 2348, SpA MFI = 2219, RA MFI = 226; p < 0.001). MAIT cells were hyporesponsive, shown by minimal upregulation of CD25 and CD69 to E. coli stimulation (control, CD25 MFI = 177, CD69 MFI = 1307; SpA, CD25 MFI = 95, CD69 MFI = 1257; RA, CD25 MFI = 0, CD69 MFI = 467; p < 0.001 and p = 0.01 respectively). In early untreated RA patients, the peripheral MAIT cell composition was altered, with reduced levels of CD161 expression, and cells were hyporesponsive to stimulation. MAIT cell dysfunction may provide a link between the microbiome and development of RA.
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cells, mait, patients, spa, cell, mfi, early, article, expression, controls, arthritis, median, untreated, google, scholar, stimulation, invariant, mucosalassociated, synovial, coli, samples, blood, peripheral, data, fixed, based, rheumatoid, compared, fig, cas, groups, activation, spondyloarthritis, differences, van, fluid, control, subsets, additional, research, composition, disease, reduced, levels, study, sfmc, cdmrtet, function, altered, access,
Topics {✒️}
disease-modifying anti-inflammatory treatments mr1–5-op-ru tetramer staining cd3+mr1-tet+ cell frequencies goat anti-migg1-af488 goat anti-rabbit-af647 goat anti-migg2a-af546 semi-invariant t-cell receptor rabbit anti-human cd20 ficoll-paque gradient centrifugation mr1-5-op-ru tetramers transitory neo-antigens derived mouse anti-human cd161 mouse anti-human vα7 menzel-gläser superfrost slides article download pdf translational research institute cd3+mr1-tet+ cells single disease-causing microbe auto-inflammatory disease development untreated rheumatoid arthritis secondary antibodies separately van der heijde ankylosing spondylitis cd4-positive related subjects live population based ra rheumatoid arthritis abbreviations 5-op-ru privacy choices/manage cookies mait cell population define live cells mr1-tetramer loaded mait cell composition small sample size full access mait cell frequencies mait cell subsets t-cell receptor diminished effector function van praet jt mait cell definition cd3+mr1-tet+ human mait cells creative commons license synovial mononuclear cells predicting arthritis outcomes arthritis res ther dutch arthritis foundation cell-derived microparticles mait cell dysfunction cell receptor heterogeneity
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- Predicting arthritis outcomes—what can be learned from the Leiden Early Arthritis Clinic?
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headline:Altered composition and phenotype of mucosal-associated invariant T cells in early untreated rheumatoid arthritis
description:Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognise bacterial metabolites presented by MHC class I-related protein 1 (MR1). Bacterial dysbiosis has been implicated in auto-inflammatory disease development. We investigated MAIT cells in early, untreated rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients. Blood and synovial fluid mononuclear cells obtained from patients (SpA/RA) and controls were stimulated with fixed Escherichia coli to provide MAIT ligand. Cells were analysed by flow cytometry and MAIT cells were identified by MR1-5-OP-RU tetramers. Synovial biopsies were studied by confocal microscopy. Peripheral and synovial CD3+ MR1-tet+ MAIT cell frequencies were comparable in all groups. MAIT cells were detected in RA and SpA synovium based on CD3, CD161 and Vα7.2 expression. Peripheral RA MAIT cells were mostly CD4+ (controls 8.3%, SpA 12.3%, RA 52.6%; p < 0.001) and CD161 expression was strongly reduced (control mean fluorescence intensity (MFI) = 2348, SpA MFI = 2219, RA MFI = 226; p < 0.001). MAIT cells were hyporesponsive, shown by minimal upregulation of CD25 and CD69 to E. coli stimulation (control, CD25 MFI = 177, CD69 MFI = 1307; SpA, CD25 MFI = 95, CD69 MFI = 1257; RA, CD25 MFI = 0, CD69 MFI = 467; p < 0.001 and p = 0.01 respectively). In early untreated RA patients, the peripheral MAIT cell composition was altered, with reduced levels of CD161 expression, and cells were hyporesponsive to stimulation. MAIT cell dysfunction may provide a link between the microbiome and development of RA.
datePublished:2019-01-05T00:00:00Z
dateModified:2019-01-05T00:00:00Z
pageStart:1
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license:http://creativecommons.org/publicdomain/zero/1.0/
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keywords:
Rheumatoid arthritis
Spondyloarthritis
Mucosal-associated invariant T cells
CD161
Rheumatology
Orthopedics
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headline:Altered composition and phenotype of mucosal-associated invariant T cells in early untreated rheumatoid arthritis
description:Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognise bacterial metabolites presented by MHC class I-related protein 1 (MR1). Bacterial dysbiosis has been implicated in auto-inflammatory disease development. We investigated MAIT cells in early, untreated rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients. Blood and synovial fluid mononuclear cells obtained from patients (SpA/RA) and controls were stimulated with fixed Escherichia coli to provide MAIT ligand. Cells were analysed by flow cytometry and MAIT cells were identified by MR1-5-OP-RU tetramers. Synovial biopsies were studied by confocal microscopy. Peripheral and synovial CD3+ MR1-tet+ MAIT cell frequencies were comparable in all groups. MAIT cells were detected in RA and SpA synovium based on CD3, CD161 and Vα7.2 expression. Peripheral RA MAIT cells were mostly CD4+ (controls 8.3%, SpA 12.3%, RA 52.6%; p < 0.001) and CD161 expression was strongly reduced (control mean fluorescence intensity (MFI) = 2348, SpA MFI = 2219, RA MFI = 226; p < 0.001). MAIT cells were hyporesponsive, shown by minimal upregulation of CD25 and CD69 to E. coli stimulation (control, CD25 MFI = 177, CD69 MFI = 1307; SpA, CD25 MFI = 95, CD69 MFI = 1257; RA, CD25 MFI = 0, CD69 MFI = 467; p < 0.001 and p = 0.01 respectively). In early untreated RA patients, the peripheral MAIT cell composition was altered, with reduced levels of CD161 expression, and cells were hyporesponsive to stimulation. MAIT cell dysfunction may provide a link between the microbiome and development of RA.
datePublished:2019-01-05T00:00:00Z
dateModified:2019-01-05T00:00:00Z
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Rheumatoid arthritis
Spondyloarthritis
Mucosal-associated invariant T cells
CD161
Rheumatology
Orthopedics
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