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Tolerogenic dendritic cells generated with dexamethasone and vitamin D3 regulate rheumatoid arthritis CD4 T cells partly via transforming growth factor-β1.

Anderson, A E, Swan, David, Wong, O Y, Buck, M, Eltherington, O, Harry, R A, Patterson, A M, Pratt, A G, Reynolds, G, Doran, J-P, Kirby, J A, Isaacs, J D and Hilkens, C M U (2016) Tolerogenic dendritic cells generated with dexamethasone and vitamin D3 regulate rheumatoid arthritis CD4 T cells partly via transforming growth factor-β1. Clinical and experimental immunology, 187 (1). pp. 113-123. ISSN 0009-9104

Item Type: Article

Abstract

Tolerogenic dendritic cells (tolDC) are a new immunotherapeutic tool for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. We have established a method to generate stable tolDC by pharmacological modulation of human monocyte-derived DC. These tolDC exert potent pro-tolerogenic actions on CD4 T cells. Lack of interleukin (IL)-12p70 production is a key immunoregulatory attribute of tolDC but does not explain their action fully. Here we show that tolDC express transforming growth factor (TGF)-β1 at both mRNA and protein levels, and that expression of this immunoregulatory cytokine is significantly higher in tolDC than in mature monocyte-derived DC. By inhibiting TGF-β1 signalling we demonstrate that tolDC regulate CD4 T cell responses in a manner that is at least partly dependent upon this cytokine. Crucially, we also show that while there is no significant difference in expression of TGF-βRII on CD4 T cells from RA patients and healthy controls, RA patient CD4 T cells are measurably less responsive to TGF-β1 than healthy control CD4 T cells [reduced TGF-β-induced mothers against decapentaplegic homologue (Smad)2/3 phosphorylation, forkhead box protein 3 (FoxP3) expression and suppression of (IFN)-γ secretion]. However, CD4 T cells from RA patients can, nonetheless, be regulated efficiently by tolDC in a TGF-β1-dependent manner. This work is important for the design and development of future studies investigating the potential use of tolDC as a novel immunotherapy for the treatment of RA.

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Depositing User: David Swan

Identifiers

Item ID: 16676
Identification Number: https://doi.org/10.1111/cei.12870
ISSN: 0009-9104
URI: http://sure.sunderland.ac.uk/id/eprint/16676
Official URL: https://academic.oup.com/cei/article/187/1/113/641...

Users with ORCIDS

ORCID for David Swan: ORCID iD orcid.org/0000-0002-6480-9621

Catalogue record

Date Deposited: 09 Oct 2023 13:12
Last Modified: 24 Apr 2024 12:45

Contributors

Author: David Swan ORCID iD
Author: A E Anderson
Author: O Y Wong
Author: M Buck
Author: O Eltherington
Author: R A Harry
Author: A M Patterson
Author: A G Pratt
Author: G Reynolds
Author: J-P Doran
Author: J A Kirby
Author: J D Isaacs
Author: C M U Hilkens

University Divisions

Faculty of Health Sciences and Wellbeing

Subjects

Sciences > Biomedical Sciences

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