Inducible deletion of in CD4 T cells inhibits kidney T cell infiltration and prevents interstitial nephritis in MRL/ lupus-prone mice.

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 conditional knockout mouse on the MRL/ lupus-prone background. We demonstrate that 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-deficient mice. deletion in CD4 T cells restricts TCR clonal repertoire and prevents kidney-infiltrating effector CD4 T cell expansion and tubulointerstitial nephritis, which has been linked to end-stage renal disease in patients with lupus nephritis.