Epigenetic dysregulation in salivary glands from patients with primary Sjögren's syndrome may be ascribed to infiltrating B cells

Thabet, Yosra; Dantec, Christelle Le; Ghedira, Ibtissem; Devauchelle, Valérie; Cornec, Divi; Pers, Jacques‐Olivier; Renaudineau, Yves

doi:10.1016/j.jaut.2013.02.002

Cited by 108 publications

(56 citation statements)

References 43 publications

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“…In addition, internal DNA demethylating factors may be also suspected such as cell cycle arrest [10], viral infection [31], and in response to cellular communication. We have recently observed that DNA demethylation in salivary glands from patients with primary Sjögren’s syndrome is related to the infiltrating B cells [32]. Last but not least, several microRNA have been reported in SLE to target DNMT1 directly or indirectly [33,34].…”

Section: Discussionmentioning

confidence: 99%

DNA methylation modulates HRES1/p28 expression in B cells from patients with Lupus

Fali¹,

Dantec²,

Thabet³

et al. 2013

Autoimmunity

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Systemic lupus erythematosus (SLE) disease is an autoimmune disease of unknown aetiology that affects predominantly women of child bearing age. Since previous studies, including ours, have demonstrated that CD4+ T cells and B cells from SLE patients are defective in their ability to methylate their DNA upon antigen stimulation, the aim of this study was to investigate whether DNA demethylation affects the transcription of HRES-1 in B cells. HRES-1 is the prototype of Human Endogenous Retrovirus (HERV) overexpressed in SLE. We have observed that SLE B cells were characterized by their incapacity to methylate the HRES-1 promoter, both in unstimulated and in anti-IgM stimulated B cells. In turn, HRES-1/p28 expression was increased in SLE B cells after B cell receptor engagement, but not in controls. In SLE B cells the Erk/DNMT1 pathway was defective. In addition, blocking the autocrine-loop of IL-6 in SLE B cells with an anti-IL-6 receptor monoclonal antibody restores DNA methylation and control of HRES-1/p28 expression became effective. As a consequence, a better understanding of HERV dysregulation in SLE reinforces our comprehension of the disease and opens new therapeutic perspectives.

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Section: Discussionmentioning

confidence: 99%

DNA methylation modulates HRES1/p28 expression in B cells from patients with Lupus

Fali¹,

Dantec²,

Thabet³

et al. 2013

Autoimmunity

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“…With this in mind, quantitative analysis of 485 577 CpG sites in pSS peripheral blood naïve CD4 + T cells and CD19 + B cells was conducted using the Illumina HumanMethylation (HM) 450 K array, leading to the characterisation of new pathways 2–4. In contrast, the EWAS study performed in minor salivary glands (MSG) showed modest variations in DNA methylation,2 5 while we have recently observed global DNA methylation alterations in salivary gland epithelial cells (SGEC) from patients with pSS leading to, among other perturbations, sicca syndrome (SS) B/La autoantigen deregulation 6 7. As the cellular heterogeneity in the MSG biopsies may explain this paradox, long-term cultured SGEC were selected to conduct an EWAS study.…”

Section: Introductionmentioning

confidence: 88%

Cell-specific epigenome-wide DNA methylation profile in long-term cultured minor salivary gland epithelial cells from patients with Sjögren's syndrome

et al. 2017

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“…It has been recently shown that salivary gland epithelial cells are globally hypomethylated compared to controls [81]. A very interesting observation was that the global gland epithelial cells hypomethylation may be attributed to B cells as treatment with the B cell depleting antibody rituximab had more methylation.…”

Section: Sjogren's Syndromementioning

confidence: 99%

Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases

Ciechomska

O’Reilly

2016

Mediators of Inflammation

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Systemic inflammatory rheumatic diseases are considered as autoimmune diseases, meaning that the balance between recognition of pathogens and avoidance of self-attack is impaired and the immune system attacks and destroys its own healthy tissue. Treatment with conventional Disease Modifying Antirheumatic Drugs (DMARDs) and/or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) is often associated with various adverse reactions due to unspecific and toxic properties of those drugs. Although biologic drugs have largely improved the outcome in many patients, such drugs still pose significant problems and fail to provide a solution to all patients. Therefore, development of more effective treatments and improvements in early diagnosis of rheumatic diseases are badly needed in order to increase patient's functioning and quality of life. The reversible nature of epigenetic mechanisms offers a new class of drugs that modulate the immune system and inflammation. In fact, epigenetic drugs are already in use in some types of cancer or cardiovascular diseases. Therefore, epigenetic-based therapeutics that control autoimmunity and chronic inflammatory process have broad implications for the pathogenesis, diagnosis, and management of rheumatic diseases. This review summarises the latest information about potential therapeutic application of epigenetic modification in targeting immune abnormalities and inflammation of rheumatic diseases.

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Epigenetic dysregulation in salivary glands from patients with primary Sjögren's syndrome may be ascribed to infiltrating B cells

Cited by 108 publications

References 43 publications

DNA methylation modulates HRES1/p28 expression in B cells from patients with Lupus

DNA methylation modulates HRES1/p28 expression in B cells from patients with Lupus

Cell-specific epigenome-wide DNA methylation profile in long-term cultured minor salivary gland epithelial cells from patients with Sjögren's syndrome

Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases

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