MeCP2 attenuates inflammation and regulates T cell phenotype via SFRP4 suppression in preeclampsia

Abstract

Preeclampsia (PE) is a major pregnancy complication characterized by an aberrant immune response. Methyl CpG binding protein 2 (MeCP2) is a potential regulator of secreted frizzled-related protein 4 (SFRP4), and both MeCP2 and SFRP4 are implicated in immune homeostasis. This study investigated the regulatory role of MeCP2/SFRP4 in immune cells in PE. A rat model of PE induced by reduced uterine perfusion pressure (RUPP) and an in vitro model using lipopolysaccharide (LPS)-stimulated HTR-8/SVneo cells were established. A co-culture system of LPS-challenged HTR-8/SVneo cells and T cells was also employed. MeCP2 expression was reduced and inversely correlated with SFRP4 levels in PE. MeCP2 overexpression suppressed Th1/Th17 differentiation while promoting Th2/Treg phenotypes, along with modulation of associated immune cytokines. It also enhanced colony formation, proliferation, migration, and invasion, while reducing apoptosis following co-culture. SFRP4 supplementation reversed the effects of MeCP2 overexpression on T cell proliferation and cytokine release. Collectively, these findings suggest that MeCP2 regulates T cell phenotype and inflammatory responses by inhibiting SFRP4, providing potential avenues for immunotherapeutic intervention in PE.