title: Protein Phosphatase 5 Contributes to the Overexpression of Epigenetically Regulated T-Lymphocyte Genes in Patients with Lupus.
abstract: OBJECTIVE
  Lupus develops when genetically predisposed people encounter certain drugs or environmental agents causing oxidative stress such as infections and sun exposure, and then typically follows a chronic relapsing course with flares triggered by the exogenous stressors. Current evidence indicates that these environmental agents can trigger lupus flares by inhibiting the replication of DNA methylation patterns during mitosis in CD4+T cells, altering the expression of genes suppressed by this mechanism that convert normal "helper" cells into auto reactive cells which promote lupus flares. How environmental stressors inhibit T cell DNA methylation though is incompletely understood. Protein phosphatase 5 (PP5) is a stress induced inhibitor of T cell ERK and JNK signaling in "senescent" CD4+CD28-T cells, also characterized by DNA demethylation and altered expression of genes that promote atherosclerosis. We tested if PP5 is increased in CD4+CD28+T cells by oxidative stress, if PP5 transfection causes overexpression of methylation sensitive genes in T cells, and if PP5 is overexpressed in lupus T cells.
  
  
  RESULTS
  PP5 was found to be overexpressed in CD4+CD28+T cells treated with H2O2and ONOO- and in T cells from lupus patients.
  
  
  CONCLUSIONS
  The results indicate that PP5 increases expression of methylation sensitive T cell genes, and may contribute to the aberrant gene expression in CD4+CD28+T cells that characterize lupus flares as well as the aberrant gene expression in CD4+CD28-T cells that promote atherosclerosis.
authors.affiliation: Eli Lilly and Company, San Diego, CA, USA; Rheumatology Division, Department of Medicine, University of Michigan, Ann Arbor MI, USA.
authors.forename: D
authors.initials: D
authors.lastname: Patel
authors.affiliation: Rheumatology Division, Department of Medicine, University of Michigan, Ann Arbor MI, USA.
authors.forename: G
authors.initials: G
authors.lastname: Gorelik
authors.affiliation: Rheumatology Division, Department of Medicine, University of Michigan, Ann Arbor MI, USA; Department of Medicine, Ann Arbor VA Medical Center, Ann Arbor MI, USA.
authors.forename: B
authors.initials: B
authors.lastname: Richardson
keywords: Atherosclerosis; DNA methylation; Lupus; Oxidative stress; Protein phosphatase 5; Signaling; T cells