Ehrenstein, MR;
Notley, CA;
Jordan, CK;
McGovern, JL;
Brown, MA;
(2017)
DNA methylation governs the dynamic regulation of inflammation by apoptotic cells during efferocytosis.
Scientific Reports
, 7
, Article 42204. 10.1038/srep42204.
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DNA methylation governs the dynamic regulation of inflammation by apoptotic cells during efferocytosis.pdf - Published Version Download (1MB) |
Abstract
Efficient clearance of apoptotic cells (AC) is pivotal in preventing autoimmunity and is a potent immunosuppressive stimulus. However, activation of cells prior to apoptosis abolishes their immunoregulatory properties. Here we show using the antigen-induced model of arthritis that the degree of DNA methylation within AC confers their immunomodulatory plasticity. DNA isolated from resting and activated AC mimicked their respective immune effects. Demethylation of DNA abrogated the protective effect of AC whereas remethylation of AC DNA reversed the effects of activation and restored the ability to inhibit inflammation. Disease suppression or lack thereof was associated with TGFβ and IL-6 production respectively. Apoptotic CD4+ T cells from patients with rheumatoid arthritis and systemic lupus erythematosus were demethylated compared to healthy controls and favoured production of IL-6 when cultured with healthy macrophages, in contrast to the TGFβ produced in response to healthy AC. Our data implicate AC DNA methylation as the molecular switch that imprints their regulatory properties.
Type: | Article |
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Title: | DNA methylation governs the dynamic regulation of inflammation by apoptotic cells during efferocytosis |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1038/srep42204 |
Publisher version: | http://dx.doi.org/10.1038/srep42204 |
Language: | English |
Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
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 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/1535366 |
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