PPP2R2B hypermethylation causes acquired apoptosis deficiency in systemic autoimmune diseases.

ABSTRACT: Chronic inflammation causes target organ damage in patients with systemic autoimmune diseases. The factors that allow this protracted response are poorly understood. We analyzed the transcriptional regulation of PPP2R2B (B55ß), a molecule necessary for the termination of the immune response, in patients with autoimmune diseases. Altered expression of B55ß conditioned resistance to cytokine withdrawal-induced death (CWID) in patients with autoimmune diseases. The impaired upregulation of B55ß was caused by inflammation-driven hypermethylation of specific cytosines located within a regulatory element of PPP2R2B preventing CTCF binding. This phenotype could be induced in healthy T cells by exposure to TNF-α. Our results reveal a gene whose expression is affected by an acquired defect, through

SUBMITTER: Madera-Salcedo IK 

PROVIDER: S-EPMC6777834 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature