Please use this identifier to cite or link to this item:
https://doi.org/10.1136/annrheumdis-2015-208992
DC Field | Value | |
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dc.title | TCR repertoire sequencing identifies synovial Treg cell clonotypes in the bloodstream during active inflammation in human arthritis | |
dc.contributor.author | Rossetti, M | |
dc.contributor.author | Spreafico, R | |
dc.contributor.author | Consolaro, A | |
dc.contributor.author | Leong, J.Y | |
dc.contributor.author | Chua, C | |
dc.contributor.author | Massa, M | |
dc.contributor.author | Saidin, S | |
dc.contributor.author | Magni-Manzoni, S | |
dc.contributor.author | Arkachaisri, T | |
dc.contributor.author | Wallace, C.A | |
dc.contributor.author | Gattorno, M | |
dc.contributor.author | Martini, A | |
dc.contributor.author | Lovell, D.J | |
dc.contributor.author | Albani, S | |
dc.date.accessioned | 2020-09-09T06:27:07Z | |
dc.date.available | 2020-09-09T06:27:07Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Rossetti, M, Spreafico, R, Consolaro, A, Leong, J.Y, Chua, C, Massa, M, Saidin, S, Magni-Manzoni, S, Arkachaisri, T, Wallace, C.A, Gattorno, M, Martini, A, Lovell, D.J, Albani, S (2017). TCR repertoire sequencing identifies synovial Treg cell clonotypes in the bloodstream during active inflammation in human arthritis. Annals of the Rheumatic Diseases 76 (2) : 435-441. ScholarBank@NUS Repository. https://doi.org/10.1136/annrheumdis-2015-208992 | |
dc.identifier.issn | 0003-4967 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/175237 | |
dc.description.abstract | Objectives The imbalance between effector and regulatory T (Treg) cells is crucial in the pathogenesis of autoimmune arthritis. Immune responses are often investigated in the blood because of its accessibility, but circulating lymphocytes are not representative of those found in inflamed tissues. This disconnect hinders our understanding of the mechanisms underlying disease. Our goal was to identify Treg cells implicated in autoimmunity at the inflamed joints, and also readily detectable in the blood upon recirculation. Methods We compared Treg cells of patients with juvenile idiopathic arthritis responding or not to therapy by using: (i) T cell receptor (TCR) sequencing, to identify clonotypes shared between blood and synovial fluid; (ii) FOXP3 Treg cell-specific demethylated region DNA methylation assays, to investigate their stability and (iii) flow cytometry and suppression assays to probe their tolerogenic functions. Results We found a subset of synovial Treg cells that recirculated into the bloodstream of patients with juvenile idiopathic and adult rheumatoid arthritis. These inflammation-associated (ia)Treg cells, but not other blood Treg cells, expanded during active disease and proliferated in response to their cognate antigens. Despite the typical inflammatory-skewed balance of immune mechanisms in arthritis, iaTreg cells were stably committed to the regulatory lineage and fully suppressive. A fraction of iaTreg clonotypes were in common with pathogenic effector T cells. Conclusions Using an innovative antigen-agnostic approach, we uncovered a population of bona fide synovial Treg cells readily accessible from the blood and selectively expanding during active disease, paving the way to non-invasive diagnostics and better understanding of the pathogenesis of autoimmunity. © 2017 Published by the BMJ Publishing Group Limited. | |
dc.publisher | BMJ Publishing Group | |
dc.source | Unpaywall 20200831 | |
dc.subject | T lymphocyte receptor beta chain | |
dc.subject | transcription factor FOXP3 | |
dc.subject | lymphocyte antigen receptor | |
dc.subject | adolescent | |
dc.subject | adult | |
dc.subject | adult disease | |
dc.subject | adult rheumatoid arthritis | |
dc.subject | amino acid sequence | |
dc.subject | Article | |
dc.subject | blood | |
dc.subject | clinical article | |
dc.subject | cohort analysis | |
dc.subject | controlled study | |
dc.subject | demethylation | |
dc.subject | DNA methylation | |
dc.subject | female | |
dc.subject | flow cytometry | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | juvenile rheumatoid arthritis | |
dc.subject | lymphocyte recirculation | |
dc.subject | male | |
dc.subject | molecular cloning | |
dc.subject | pathogenesis | |
dc.subject | prospective study | |
dc.subject | protein stability | |
dc.subject | regulatory T lymphocyte | |
dc.subject | rheumatoid arthritis | |
dc.subject | synovial fluid | |
dc.subject | T lymphocyte subpopulation | |
dc.subject | child | |
dc.subject | cytology | |
dc.subject | genetics | |
dc.subject | immunology | |
dc.subject | juvenile rheumatoid arthritis | |
dc.subject | preschool child | |
dc.subject | regulatory T lymphocyte | |
dc.subject | rheumatoid arthritis | |
dc.subject | synovium | |
dc.subject | T lymphocyte receptor gene | |
dc.subject | young adult | |
dc.subject | Adolescent | |
dc.subject | Adult | |
dc.subject | Arthritis, Juvenile | |
dc.subject | Arthritis, Rheumatoid | |
dc.subject | Child | |
dc.subject | Child, Preschool | |
dc.subject | DNA Methylation | |
dc.subject | Female | |
dc.subject | Flow Cytometry | |
dc.subject | Genes, T-Cell Receptor beta | |
dc.subject | Humans | |
dc.subject | Male | |
dc.subject | Receptors, Antigen, T-Cell | |
dc.subject | Synovial Fluid | |
dc.subject | Synovial Membrane | |
dc.subject | T-Lymphocytes, Regulatory | |
dc.subject | Young Adult | |
dc.type | Article | |
dc.contributor.department | DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL) | |
dc.contributor.department | BIOLOGICAL SCIENCES | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1136/annrheumdis-2015-208992 | |
dc.description.sourcetitle | Annals of the Rheumatic Diseases | |
dc.description.volume | 76 | |
dc.description.issue | 2 | |
dc.description.page | 435-441 | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
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