Epigenetic Mechanisms in Sjögren’s Syndrome - European Medical Journal

Epigenetic Mechanisms in Sjögren’s Syndrome

Rheumatology
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Authors:
Christelle Le Dantec,1 Amandine Charras,1 Anne Bordron,1 Wesley H. Brooks,2 *Yves Renaudineau1,3
Disclosure:

The authors have declared no conflicts of interest.

Acknowledgements:

This work was supported by the ‘Région Bretagne’, the ‘Association Française Gougerot-Sjögren et des Syndromes Secs’, and by the ‘Institut Français pour la Recherche Odontologique’. We are also grateful to Simone Forest and Geneviève Michel for their help in typing the paper. The research leading to these results received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115565, resources of which are composed of financial contributions from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in-kind contribution.

Received:
03.03.16
Accepted:
11.07.16
Citation:
EMJ. ;1[5]:21-28. DOI/10.33590/emj/10311584. https://doi.org/10.33590/emj/10311584.
Keywords:
Sjögren’s syndrome (SS), epigenetics, DNA methylation, histone acetylation, endogenous retrovirus

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

Abstract

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune epithelitis and recent advances in our comprehension of its pathophysiology strongly suggest a multi-step process that involves environmental factors (e.g. chronic viral infection, drugs), followed by deregulation of the epigenetic machinery (e.g. DNA demethylation, histone modifications, microRNAs), which in turn specifically affects lymphocytes and epithelial cells leading to an aberrant inflammation. This process is amplified in the case of genetic mutations. As a consequence, autoreactive lymphocytes and autoantigens are produced leading to the development of autoantibodies. Moreover, it was observed that epigenetic modifications in pSS could be reversed, thus providing arguments to suggest that therapeutic strategies targeting the epigenetic deregulation and in particular the PKC-delta/Erk/DNMT1 pathway would be effective in pSS.

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