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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Epigenetic dysregulation in salivary glands from patients with primary Sjögren's syndrome may be ascribed to infiltrating B cells
Journal of Autoimmunity, Volume 41, Year 2013
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Description
Sjögren's syndrome (SS) is an autoimmune exocrinopathy characterized by an epithelium injury with dense lymphocytic infiltrates, mainly composed of activated T and B cells. Present at the interface of genetic and environmental risk factors, DNA methylation is suspected to play a key role in SS. To clarify this point, global DNA methylation was tested within salivary gland epithelial cells (SGEC), peripheral T cells and B cells from SS patients. Global DNA methylation was reduced in SGEC from SS patients, while no difference was observed in T and B cells. SGEC demethylation in SS patients was associated with a 7-fold decrease in DNA methyl transferase (DNMT) 1 and a 2-fold increase in Gadd45-alpha expression. The other DNA methylation/demethylation partners, tested by real time PCR (DNMT3a/b, PCNA, UHRF1, MBD2, and MBD4), were not different. Interestingly, SGEC demethylation may be attributed in part to the infiltrating B cells as suspected in patients treated with anti-CD20 antibodies to deplete B cells. Such hypothesis was confirmed using co-culture experiments with human salivary gland cells and B cells. Furthermore, B cell-mediated DNA demethylation could be ascribed to an alteration of the PKC delta/ERK/DNMT1 pathway. As a consequence, part of the SGEC dysfunction in SS may be linked to epigenetic modifications, thus opening new therapeutic perspectives in SS. © 2013 Elsevier Ltd.
Authors & Co-Authors
Thabet, Yosra
France, Brest
Lymphocyte b et Auto Immunité Lbai
Tunisia, Monastir
Faculté de Pharmacie de Monastir
Le Dantec, Christelle
France, Brest
Lymphocyte b et Auto Immunité Lbai
Ghédira, Ibtissem
Tunisia, Monastir
Faculté de Pharmacie de Monastir
Devauchelle-Pensec, Valérie
France, Brest
Lymphocyte b et Auto Immunité Lbai
France, Brest
Hopital de la Cavale Blanche
Cornec, Divi Y.K.
France, Brest
Lymphocyte b et Auto Immunité Lbai
France, Brest
Hopital de la Cavale Blanche
Pers, Jacques-Olivier Olivier
France, Brest
Lymphocyte b et Auto Immunité Lbai
Renaudineau, Yves
France, Brest
Lymphocyte b et Auto Immunité Lbai
France, Brest
Hopital Morvan
Statistics
Citations: 105
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1016/j.jaut.2013.02.002
ISSN:
08968411
e-ISSN:
10959157
Research Areas
Genetics And Genomics
Violence And Injury