title: DNA methylation modulates HRES1/p28 expression in B cells from patients with Lupus.
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.
authors.affiliation: EA2216 "Immunology, Pathology and Immunotherapy", University of Brittany, SFR ScinBios and Labex Igo "Immunotherapy Graft, Oncology" , Brest , France .
authors.forename: Tinhinane
authors.initials: T
authors.lastname: Fali
authors.forename: Christelle
authors.initials: C
authors.lastname: Le Dantec
authors.forename: Yosra
authors.initials: Y
authors.lastname: Thabet
authors.forename: Sandrine
authors.initials: S
authors.lastname: Jousse
authors.forename: Catherine
authors.initials: C
authors.lastname: Hanrotel
authors.forename: Pierre
authors.initials: P
authors.lastname: Youinou
authors.forename: Wesley H
authors.initials: WH
authors.lastname: Brooks
authors.forename: Andras
authors.initials: A
authors.lastname: Perl
authors.forename: Yves
authors.initials: Y
authors.lastname: Renaudineau
mesh_terms: D000328:Adult; D034961:Antigens, Nuclear / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019175:DNA Methylation; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D019947:Receptors, Interleukin-6 / Q000276:immunology / Q000378:metabolism; D012191:Retroviridae Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D001324:Autoantigens; C096557:HRES-1 p28 protein, human retroviral element; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D012191:Retroviridae Proteins
keywords: B cells; DNA methylation; Erk; HRES-1; IL-6; systemic lupus erythematosus