UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

CD4 T Cell Dysregulation In Psoriatic Arthritis Reveals A Regulatory Role For IL-22

Ehrenstein, MR; Ezeonyeji, A; Baldwin, H; Vukmanovic-Stejic, M; (2017) CD4 T Cell Dysregulation In Psoriatic Arthritis Reveals A Regulatory Role For IL-22. Frontiers in Immunology , 8 , Article 1403. 10.3389/fimmu.2017.01403. Green open access

[img]
Preview
Text
Ehrenstein_CD4 T-Cell Dysregulation in Psoriatic Arthritis Reveals a Regulatory Role for IL-22.pdf - Published version

Download (3MB) | Preview

Abstract

Dysregulation of interleukin-22 (IL-22) has been associated with autoimmune diseases but divergent effects upon inflammation have hampered efforts to define its contribution to pathogenesis. Here, we examined the role of IL-22 in patients with psoriatic arthritis (PsA). In the peripheral blood of PsA patients, there was a decrease in IL-22+CD4+ T cells compared with healthy controls resulting in a heightened CD4+ IFNγ+/IL-22+ ratio accompanied by diminished CCR6 expression. IL-22 expressing cells were depleted primarily from the central memory CD4 T-cell subset in PsA patients. Paradoxically IL-22 and particularly interferon-gamma (IFNγ) production were elevated within a CD4+ T-cell subset with phenotypic markers characteristic of naïve T  cells (CD3+CD4+CD27+CD45RA+CCR7+CD95−IL-2Rβ−) from PsA patients with the highest IFNγ+/IL-22+ ratio of all the CD4 subsets. These unconventional “naïve” CD4+ T cells from PsA patients displayed some phenotypic and functional characteristics of memory cells including a marked proliferative response. Increased IFNγ production from these unconventional “naïve” T cells from PsA patients promoted greater expression of the chemo-attractant CXCL9 by HaCaT keratinocytes compared with their healthy counterparts. Treatment with anti-TNF therapy reversed these abnormalities in this T-cell subset though did not affect the frequency of IL-22+ T cells overall. Furthermore, blockade of IL-22 enhanced the IFNγ mediated release of CXCL-9. These results reveal CD4+ T-cell dysregulation in patients with PsA which can be reversed by anti-TNF and highlight the regulatory properties of IL-22 with important implications for therapeutic approaches that inhibit its production.

Type: Article
Title: CD4 T Cell Dysregulation In Psoriatic Arthritis Reveals A Regulatory Role For IL-22
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2017.01403
Publisher version: http://doi.org/10.3389/fimmu.2017.01403
Language: English
Additional information: © 2017 Ezeonyeji, Baldwin, Vukmanovic-Stejic and Ehrenstein. 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: IL-22, interferon-gamma, naïve T cell, psoriatic arthritis, anti-TNF
UCL classification: UCL
UCL > Provost and Vice Provost Offices
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 Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10024668
Downloads since deposit
27Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item