Inducible deletion of <i>Ezh2</i> in CD4⁺ T cells inhibits kidney T cell infiltration and prevents interstitial nephritis in MRL/<i>lpr</i> lupus-prone mice.

ABSTRACT: Systemic lupus erythematosus is a remitting relapsing autoimmune disease characterized by autoantibody production and multi-organ involvement. T cell epigenetic dysregulation plays an important role in the pathogenesis of lupus. We have previously demonstrated upregulation of the key epigenetic regulator EZH2 in CD4⁺ T cells isolated from lupus patients. To further investigate the role of EZH2 in the pathogenesis of lupus, we generated a tamoxifen-inducible CD4⁺ T cell Ezh2 conditional knockout mouse on the MRL/lpr lupus-prone background. We demonstrate that Ezh2 deletion abrogates lupus-like disease and prevents T cell differentiation. Single-cell analysis suggests impaired T cell function and activation of programmed cell death pathways in EZH2-

SUBMITTER: Zheng X 

PROVIDER: S-EPMC11532947 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature