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CD161(+) Tconv and CD161(+) Treg Share a Transcriptional and Functional Phenotype despite Limited Overlap in TCR beta Repertoire

Duurland, CL; Brown, CC; O'Shaughnessy, RFL; Wedderburn, LR; (2017) CD161(+) Tconv and CD161(+) Treg Share a Transcriptional and Functional Phenotype despite Limited Overlap in TCR beta Repertoire. Frontiers in Immunology , 8 , Article 103. 10.3389/fimmu.2017.00103. Green open access

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Abstract

Human regulatory T cells (Treg) are important in immune regulation, but can also show plasticity in specific settings. CD161 is a lectin-like receptor and its expression identifies an effector-like Treg population. Here, we determined how CD161+ Treg relate to CD161+ conventional T cells (Tconv). Transcriptional profiling identified a shared transcriptional signature between CD161+ Tconv and CD161+ Treg, which is associated with T helper (Th)1 and Th17 cells, and tissue homing, including high expression of gut-homing receptors. Upon retinoic acid (RA) exposure, CD161+ T cells were more enriched for CCR9+ and integrin α4+β7+ cells than CD161− T cells. In addition, CD161+ Tconv and CD161+ Treg were enriched at the inflamed site in autoimmune arthritis, and both CD161+ and CD161− Treg from the inflamed site were suppressive in vitro. CD161+ T cells from the site of autoimmune arthritis showed a diminished gut-homing phenotype and blunted response to RA suggesting prior imprinting by RA in the gut or at peripheral sites rather than during synovial inflammation. TCRβ repertoires of CD161+ and CD161− Tconv and Treg from blood showed limited overlap whereas there was clear overlap between CD161+ and CD161− Tconv, and CD161+ and CD161− Treg from the inflamed site suggesting that the inflamed environment may alter CD161 levels, potentially contributing to disease pathogenesis.

Type: Article
Title: CD161(+) Tconv and CD161(+) Treg Share a Transcriptional and Functional Phenotype despite Limited Overlap in TCR beta Repertoire
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2017.00103
Publisher version: http://doi.org/10.3389/fimmu.2017.00103
Language: English
Additional information: Copyright © 2017 Duurland, Brown, O’Shaughnessy and Wedderburn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: CD161, conventional T cells (Tconv), regulatory T cells (Treg), transcriptome, juvenile idiopathic arthritis (JIA), tissue homing, T cell receptor (TCR), retinoic acid
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1551442
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