Please use this identifier to cite or link to this item: https://doi.org/10.1136/annrheumdis-2015-208992
Title: TCR repertoire sequencing identifies synovial Treg cell clonotypes in the bloodstream during active inflammation in human arthritis
Authors: 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 
Keywords: T lymphocyte receptor beta chain
transcription factor FOXP3
lymphocyte antigen receptor
adolescent
adult
adult disease
adult rheumatoid arthritis
amino acid sequence
Article
blood
clinical article
cohort analysis
controlled study
demethylation
DNA methylation
female
flow cytometry
human
human cell
juvenile rheumatoid arthritis
lymphocyte recirculation
male
molecular cloning
pathogenesis
prospective study
protein stability
regulatory T lymphocyte
rheumatoid arthritis
synovial fluid
T lymphocyte subpopulation
child
cytology
genetics
immunology
juvenile rheumatoid arthritis
preschool child
regulatory T lymphocyte
rheumatoid arthritis
synovium
T lymphocyte receptor gene
young adult
Adolescent
Adult
Arthritis, Juvenile
Arthritis, Rheumatoid
Child
Child, Preschool
DNA Methylation
Female
Flow Cytometry
Genes, T-Cell Receptor beta
Humans
Male
Receptors, Antigen, T-Cell
Synovial Fluid
Synovial Membrane
T-Lymphocytes, Regulatory
Young Adult
Issue Date: 2017
Publisher: BMJ Publishing Group
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
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.
Source Title: Annals of the Rheumatic Diseases
URI: https://scholarbank.nus.edu.sg/handle/10635/175237
ISSN: 0003-4967
DOI: 10.1136/annrheumdis-2015-208992
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