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Article Dans Une Revue Autoimmunity Année : 2014

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

Résumé

Abstract 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.

Domaines

Immunologie

Dates et versions

hal-00996373 , version 1 (26-05-2014)

Identifiants

Citer

Tinhinane Fali, Christelle Le Dantec, Yosra Thabet, Sandrine Jousse, Catherine Hanrotel, et al.. DNA methylation modulates HRES1/p28 expression in B cells from patients with Lupus.. Autoimmunity, 2014, 47 (4), pp.265-71. ⟨10.3109/08916934.2013.826207⟩. ⟨hal-00996373⟩

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