Epigenetic modifications in salivary glands from patients with Sjögren's syndrome affect cytokeratin 19 expression

Authors

  • O.D. Konsta 1-Research Unit EA2216 Immunology, Pathology and Immunotherapy, SFR ScinBios and Labex Igo “Immunotherapy Graft, Oncology”, Réseau épigénétique du cancéropole Grand Ouest, European University of Brittany, Brest, France 2-Department of Pathophysiology, School of Medicine, National University of Athens, 75 Mikras Asias street, Athens 11527, Greece
  • A. Charras Research Unit EA2216 Immunology, Pathology and Immunotherapy, SFR ScinBios and Labex Igo “Immunotherapy Graft, Oncology”, Réseau épigénétique du cancéropole Grand Ouest, European University of Brittany, Brest, France
  • C. Le Dantec Research Unit EA2216 Immunology, Pathology and Immunotherapy, SFR ScinBios and Labex Igo “Immunotherapy Graft, Oncology”, Réseau épigénétique du cancéropole Grand Ouest, European University of Brittany, Brest, France
  • E. Kapsogeorgeou Department of Pathophysiology, School of Medicine, National University of Athens, 75 Mikras Asias street, Athens 11527, Greece
  • A. Bordron Research Unit EA2216 Immunology, Pathology and Immunotherapy, SFR ScinBios and Labex Igo “Immunotherapy Graft, Oncology”, Réseau épigénétique du cancéropole Grand Ouest, European University of Brittany, Brest, France
  • W.H. Brooks Department of Chemistry, University of South Florida, Tampa, Florida, USA
  • A.G. Tzioufas Department of Pathophysiology, School of Medicine, National University of Athens, 75 Mikras Asias street, Athens 11527, Greece
  • J O Pers Université de Bretagne Occidentale, Brest
  • Y. Renaudineau Laboratory of Immunology and Immunotherapy, Brest University Medical School, CHU Morvan, Brest, France

Keywords:

Sjögren’s syndrome, DNA methylation, HERV, epithelial cells

Abstract

Sjögren’s syndrome (SS) is a chronic autoimmune epithelitis, and several lines of experiments indicate that multifactorial factors contribute to salivary gland epithelial cells (SGEC) dysfunctions including a combination of environmental factors, lymphocytic infiltrations, genetic predispositions as well as epigenetic defects. Such statement is reinforced by the observation that global DNA methylation (5MeCyt) is altered in minor salivary glands from pSS patients and that such defect is associated cytokeratin 19 (KRT19) overexpression. An epigenetic deregulation of the KRT19 gene was further tested by treating the human salivary gland (HSG) cell line with the DNA demethylating agent 5-azacytidin, and with the histone acetylase inhibitor trichostatin A. Blocking DNA methylation, but not histone acetylation, with 5-azacytidin was associated with KRT19 overexpression at both transcriptional and protein level. Next, analysis of the CpG genome-wide methylome array in the KTR19 locus from long term cultured SGEC obtained from 8 pSS patients revealed a more reduced DNA methylation level in those patients with defective global DNA methylation. Altogether, our data, therefore, suggest that alteration of DNA methylation in SGEC may contribute to pSS pathophysiology in part by controlling the expression of KRT19.

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Published

2016-06-28

Issue

Vol. 53 No. 1 (2016)

Section

Articles

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